Polynucleotides and polypeptide sequences involved in cancer

ABSTRACT

The present invention relates to polynucleotide and polypeptide sequences which are differentially expressed in cancer cells compared to normal cells. The present invention more particularly relates to the use of these sequences in the diagnosis, prognosis or treatment of cancer and in the detection of cancer cells.

PRIORITY CLAIM

This patent application is a continuation of U.S. Ser. No. 14/690,562filed Apr. 20, 2015, which is a continuation of U.S. Ser. No. 13/490,857filed on Jun. 7, 2012, which is a divisional of U.S. Ser. No. 12/305,648filed on Nov. 6, 2009 now U.S. Pat. No. 8,216,582 which is a nationalstage filing under 35 U.S.C. § 371 of international application No.PCT/CA2007/001134 filed on Jun. 22, 2007 which claimed priority to U.S.provisional application No. 60/815,829 filed Jun. 23, 2006 and U.S.provisional application No. 60/874,471 filed on Dec. 13, 2006. Theentire contents of each of these priority applications are incorporatedherein by reference.

SEQUENCE LISTING

In accordance with 37 C.F.R. § 1.52(e)(5), a Sequence Listing in theform of a computer readable text file, submitted on a compact disk (inaccordance to 37 C.F.R. § 1.52(e)) entitled:“ADC_11504_220C1_SEQUENCELISTING_ST25.txt”, created on Aug. 21, 2018 of281,730 bytes) and is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to polynucleotide and polypeptidesequences which are differentially expressed in cancer compared tonormal cells. The present invention more particularly relates to the useof these sequences in the diagnosis, prognosis or treatment of cancerand in the detection of cancer cells.

BACKGROUND OF THE INVENTION

Among gynecologic malignancies, ovarian cancer accounts for the highesttumor-related mortality in women in the United States (Jemal et al.,2005). It is the fourth leading cause of cancer-related death in womenin the U.S (Menon et al., 2005). The American Cancer Society estimated atotal of 22,220 new cases in 2005 and attributed 16,210 deaths to thedisease (Bonome et al., 2005). For the past 30 years, the statisticshave remained largely the same—the majority of women who develop ovariancancer will die of this disease (Chambers and Vanderhyden, 2006). Thedisease carries a 1:70 lifetime risk and a mortality rate of >60%(Chambers and Vanderhyden, 2006). The high mortality rate is due to thedifficulties with the early detection of ovarian cancer when themalignancy has already spread beyond the ovary. Indeed, >80% of patientsare diagnosed with advanced staged disease (stage III or IV) (Bonome etal., 2005). These patients have a poor prognosis that is reflected in<45% 5-year survival rate, although 80% to 90% will initially respond tochemotherapy (Berek et al., 2000). This increased success compared to20% 5-year survival rate years earlier is, at least in part, due to theability to optimally debulk tumor tissue when it is confined to theovaries, which is a significant prognostic factor for ovarian cancer(Bristow R. E., 2000 and Brown et al., 2004). In patients who arediagnosed with early disease (stage I), the 5-yr survival rangesfrom >90 (Chambers and Vanderhyden, 2006).

Ovarian cancer comprises a heterogeneous group of tumors that arederived from the surface epithelium of the ovary or from surfaceinclusions. They are classified into serous, mucinous, endometrioid,clear cell, and Brenner (transitional) types corresponding to thedifferent types of epithelia in the organs of the female reproductivetract (Shih and Kurman, 2005). Of these, serous tumors account for ˜60%of the ovarian cancer cases diagnosed. Each histologic subcategory isfurther divided into three groups: benign, intermediate (borderlinetumor or low malignancy potential (LMP)), and malignant, reflectingtheir clinical behavior (Seidman et al., 2002). LMP represents 10% to15% of tumors diagnosed as serous and is a conundrum as they displayatypical nuclear structure and metastatic behavior, yet they areconsiderably less aggressive than high-grade serous tumors. The 5-yearsurvival for patients with LMP tumors is 95% in contrast to a <45%survival for advanced high-grade disease over the same period (Berek etal., 2000).

Despite improved knowledge of the etiology of the disease, aggressivecytoreductive surgery, and modern combination chemotherapy, there hasbeen only little change in mortality. Poor outcomes have been attributedto (1) lack of adequate screening tests for early disease detection, incombination with only subtle presentation of symptoms at thisstage—diagnosis is frequently being made only after progression to laterstages, at which point the peritoneal dissemination of the cancer limitseffective treatment and (2) the frequent development of resistance tostandard chemotherapeutic strategies limiting improvement in the 5-yearsurvival rate of patients. The initial chemotherapy regimen for ovariancancer includes the combination of carboplatin (Paraplatin) andpaclitaxel (taxol). Years of clinical trials have proved thiscombination to be most effective after effective surgery—reduces tumorvolume in about 80% of the women with newly diagnosed ovarian cancer and40% to 50% will have complete regression—but studies continue to lookfor ways to improve it. Recent abdominal infusion of chemotherapeuticsto target hard-to-reach cells in combination with intravenous deliveryhas increased the effectiveness. However, severe side effects often leadto an incomplete course of treatment. Some other chemotherapeutic agentsinclude doxorubicin, cisplatin, cyclophosphamide, bleomycin, etoposide,vinblastine, topotecan hydrochloride, ifosfamide, 5-fluorouracil andmelphalan. The excellent survival rates for women with early stagedisease receiving chemotherapy provide a strong rationale for researchefforts to develop strategies to improve the detection of ovariancancer. Furthermore, the discovery of new ovarian cancer-relatedbiomarkers will lead to the development of more effective therapeuticstrategies with minimal side effects for the future treatment of ovariancancer.

Presently, the diagnosis of ovarian cancer is accomplished, in part,through routine analysis of the medical history of patients and byperforming physical, ultrasound and x-ray examinations, andhematological screening. Two alternative strategies have been reportedfor early hematological detection of serum biomarkers. One approach isthe analysis of serum samples by mass spectrometry to find proteins orprotein fragments of unknown identity that detect the presence orabsence of cancer (Mor et al., 2005 and Kozak et al., 2003). However,this strategy is expensive and not broadly available. Alternatively, thepresence or absence of known proteins/peptides in the serum is beingdetected using antibody microarrays, ELISA, or other similar approaches.Serum testing for a protein biomarker called CA-125 (cancer antigen-125)has long been widely performed as a marker for ovarian cancer. However,although ovarian cancer cells may produce an excess of these proteinmolecules, there are some other cancers, including cancer of thefallopian tube or endometrial cancer (cancer of the lining of theuterus), 60% of people with pancreatic cancer, and 20%-25% of peoplewith other malignancies with elevated levels of CA-125. The CA-125 testonly returns a true positive result for about 50% of Stage I ovariancancer patients and has a80% chance of returning true positive resultsfrom stage II, III, and IV ovarian cancer patients. The other 20% ofovarian cancer patients do not show any increase in CA-125concentrations. In addition, an elevated CA-125 test may indicate otherbenign activity not associated with cancer, such as menstruation,pregnancy, or endometriosis. Consequently, this test has very limitedclinical application for the detection of early stage disease when it isstill treatable, exhibiting a positive predictive value (PPV) of <10%.And, even with the addition of ultrasound screening to CA-125, the PPVonly improves to around 20% (Kozak et al., 2003). Thus, this test is notan effective screening test.

Other studies have yielded a number of biomarker combinations withincreased specificity and sensitivity for ovarian cancer relative toCA-125 alone (McIntosh et al., 2004, Woolas et al., 1993, Schorge et.,2004). Serum biomarkers that are often elevated in women with epithelialovarian cancer, but not exclusively, include carcinoembryonic antigen,ovarian cystadenocarcinoma antigen, lipidassociated sialic acid, NB/70,TAG72.3, CA-15.3, and CA-125. Unfortunately, although this approach hasincreased the sensitivity and specificity of early detection, publishedbiomarker combinations still fail to detect a significant percentage ofstage I/II epithelial ovarian cancer. Another study (Elieser et al.,2005) measured serum concentrations of 46 biomarkers including CA-125and amongst these, 20 proteins in combination correctly recognized morethan 98% of serum samples of women with ovarian cancer compared to otherbenign pelvic disease. Although other malignancies were not included inthis study, this multimarker panel assay provided the highest diagnosticpower for early detection of ovarian cancer thus far.

Additionally, with the advent of differential gene expression analysistechnologies, for example DNA microarrays and subtraction methods, manygroups have now reported large collections of genes that are upregulatedin epithelial ovarian cancer (United States Patent Application publishedunder numbers; 20030124579, 20030087250, 20060014686, 20060078941,20050095592, 20050214831, 20030219760, 20060078941, 20050214826).However, the clinical utilities with respect to ovarian cancer of one orcombinations of these genes are not as yet fully determined.

There is a need for new tumor biomarkers for improving diagnosis and/orprognosis of cancer. In addition, due to the genetic diversity oftumors, and the development of chemoresistance by many patients, thereexists further need for better and more universal therapeutic approachesfor the treatment of cancer. Molecular targets for the development ofsuch therapeutics may preferably show a high degree of specificity forthe tumor tissues compared to other somatic tissues, which will serve tominimize or eliminate undesired side effects, and increase the efficacyof the therapeutic candidates.

This present invention tries to address these needs and other needs.

SUMMARY OF THE INVENTION

In accordance with the present invention, there is provided newpolynucleotide sequences and new polypeptide sequences as well ascompositions, antibodies specific for these sequences, vectors and cellscomprising a recombinant form of these new sequences.

The present invention also provides methods of detecting cancer cellsusing single or multiple polynucleotides and/or polypeptide sequenceswhich are specific to these tumor cells. Some of the polynucleotidesand/or polypeptides sequences provided herein are differentiallyexpressed in ovarian cancer compared to normal cells and may also beused to distinguish between malignant ovarian cancer and an ovariancancer of a low malignancy potential and/or a normal state (individualfree of ovarian cancer).

Also encompassed by the present invention are diagnostic methods,prognostic methods, methods of detection, kits, arrays, libraries andassays which comprises one or more polypeptide and/or polynucleotidesequences or antibodies described herein as well as new therapeuticavenues for cancer treatment.

The Applicant has come to the surprising discovery that polynucleotideand/or polypeptide sequences described herein are preferentiallyupregulated in malignant ovarian cancer compared to low malignancypotential ovarian cancer and/or compared to normal cells. Moreinterestingly, some of these sequences appear to be overexpressed inlate stage ovarian cancer.

The Applicant has also come to the surprising discovery that some of thesequences described herein are not only expressed in ovarian cancercells but in other cancer cells such as cells from breast cancer,prostate cancer, renal cancer, colon cancer, lung cancer, melanoma,leukemia and from cancer of the central nervous system. As such, severalof these sequences, either alone or in combination may representuniversal tumor markers. Therefore, some NSEQs and PSEQs describedherein not only find utility in the field of ovarian cancer detectionand treatment but also in the detection and treatment of other types oftumors

Therefore, using NSEQs or PSEQs of the present invention, one mayreadily identify a cell as being cancerous. As such NSEQs or PSEQs maybe used to identify a cell as being a ovarian cancer cell, a prostatecancer cell, a breast cancer cell, a lung cancer cell, a colon cancercell, a renal cancer cell, a cell from a melanoma, a leukemia cell or acell from a cancer of the central nervous system.

Even more particularly, NSEQs or PSEQs described herein may be used toidentify a cell as being a malignant ovarian cancer or a low malignantpotential ovarian cancer.

The presence of some NSEQs or PSEQs in ovarian cancer cell maypreferentially be indicative that the ovarian cancer is of the malignanttype. Some NSEQs or PSEQs of the present invention may also moreparticularly indicate that the cancer is a late-stage malignant ovariancancer.

The NSEQs or PSEQs may further be used to treat cancer or to identifycompounds useful in the treatment of cancer including, ovarian cancer(i.e., LMP and/or malignant ovarian cancer), prostate cancer, breastcancer, lung cancer, colon cancer, renal cancer, melanoma, leukemia orcancer of the central nervous system.

As used herein and in some embodiments of the invention, the term “NSEQ”refers generally to polynucleotides sequences comprising or consistingof any one of SEQ. ID. NOs:1 to 49, and 169 (e.g., an isolated form) orcomprising or consisting of a fragment of any one of SEQ. ID. NOs: 1 to49 and 169. The term “NSEQ” more particularly refers to a polynucleotidesequence comprising or consisting of a transcribed portion of any one ofSEQ. ID. NOs:1 to 49 and 169, which may be, for example, free ofuntranslated or untranslatable portion(s) (i.e., a coding portion of anyone of SEQ ID Nos.: 1-49 and 169). The term “NSEQ” additionally refersto a sequence substantially identical to any one of the above and moreparticularly substantially identical to polynucleotide sequencecomprising or consisting of a transcribed portion of any one of SEQ. ID.NOs:1 to 49 and 169, which may be, for example, free of untranslated oruntranslatable portion(s). The term “NSEQ” additionally refers to anucleic acid sequence region of any one of SEQ. ID. NOs:1 to 49 and 169which encodes or is able to encode a polypeptide. The term “NSEQ” alsorefers to a polynucleotide sequence able to encode any one of thepolypeptides described herein or a polypeptide fragment of any one ofthe above. Finally, the term “NSEQ” refers to a sequence substantiallycomplementary to any one of the above.

In other embodiments of the invention such as those which relate todetection and/or treatment of cancers other than ovarian cancer, NSEQmay also relates to SEQ ID NO.:50 including any polynucleotidecomprising or consisting of SEQ. ID. NO:50 (e.g., an isolated form) orcomprising or consisting of a fragment of any one of SEQ. ID. NO:50,such as a polynucleotide sequence comprising or consisting of atranscribed portion of any one of SEQ. ID. NO:50, which may be, forexample, free of untranslated or untranslatable portion(s) (i.e., acoding portion of SEQ. ID. NO:50). The term “NSEQ” additionally refersto a sequence substantially identical to any one of the above and moreparticularly substantially identical to polynucleotide sequencecomprising or consisting of a transcribed portion of SEQ. ID. NO:50,which may be, for example, free of untranslated or untranslatableportion(s). The term “NSEQ” additionally refers to a nucleic acidsequence region of SEQ. ID. NO:50 which encodes or is able to encode apolypeptide. Finally, the term “NSEQ” refers to a sequence substantiallycomplementary to any one of the above.

As such, in embodiments of the invention NSEQ encompasses, for example,SEQ. ID. NOs:1 to 49, 50 and 169 and also encompasses polynucleotidesequences which comprises, are designed or derived from SEQ. ID. NOs:1to 49, 50 or 169. Non-limiting examples of such sequences includes, forexample, SEQ ID NOs.: 103-150 or 151-152.

The term “inhibitory NSEQ” generally refers to a sequence substantiallycomplementary to any one of SEQ. ID. NOs:1 to 49, 50 or 169,substantially complementary to a fragment of any one of SEQ. ID. Nos: 1to 49, 50 or 169, substantially complementary to a sequencesubstantially identical to SEQ. ID. NOs:1 to 49, 50 or 169 and moreparticularly, substantially complementary to a transcribed portion ofany one of SEQ. ID. NOs:1 to 49, 50 or 169 (e.g., which may be free ofunstranslated or untranslatable portion) and which may have attenuatingor even inhibitory action against the transcription of a mRNA or againstexpression of a polypeptide encoded by a corresponding SEQ ID NOs.:1 to49, 50 or 169. Suitable “inhibitory NSEQ” may have for example andwithout limitation from about 10 to about 30 nucleotides, from about 10to about 25 nucleotides or from about 15 to about 20 nucleotides.

As used herein the term “PSEQ” refers generally to each and everypolypeptide sequences mentioned herein such as, for example, anypolypeptide sequences encoded (putatively encoded) by any one of NSEQdescribed herein (e.g., any one of SEQ. ID. NOs:1 to 49 or 169)including their isolated or substantially purified form. Therefore, inembodiments of the invention, a polypeptide comprising or consisting ofany one of SEQ. ID. NOs:51 to 88 or 170 including variants (e.g., anisolated natural protein variant), analogs, derivatives and fragmentsthereof are collectively referred to herein as “PSEQ”. In otherembodiments of the invention, such as those related to detection and/ortreatment of cancers other than ovarian cancer, PSEQ also refers topolypeptide comprising or consisting of SEQ ID NO.:89 including variants(e.g., an isolated natural protein variant), analogs, derivatives andfragments.

Some of the NSEQs or PSEQs described herein have been previouslycharacterized for purposes other than those described herein. As suchdiagnostics and therapeutics which are known to target those NSEQs orPSEQs (e.g., antibodies and/or inhibitors) may thus now be applied forinhibition of these NSEQ or PSEQ in the context of treatment of ovariancancer, prostate cancer, renal cancer, colon cancer, lung cancer,melanoma, leukemia or cancer of the central nervous system. The use ofthese known therapeutics and diagnostics for previously undisclosedutility such as those described herein is encompassed by the presentinvention.

For example, antibodies capable of binding to folate receptor-1 may thusbe used for specific binding of tumor cells other than ovarian cancercells, such as breast cancer, prostate cancer, renal cancer, coloncancer, lung cancer, melanoma, leukemia and from cancer of the centralnervous system. As such the use of antibodies and/or inhibitors offolate receptor-1 (e.g., CB300638, CB300945 which areCyclopenta[g]quinazoline-based Thymidylate Synthase Inhibitor, thosedescribed in US20040242606, US20050009851, etc.) in the use of treatmentof prostate cancer, renal cancer, colon cancer, lung cancer, melanoma,leukemia and cancer of the central nervous system is encompassed by thepresent invention.

Non-Limitative Exemplary Embodiments of the Invention Use of NSEQ as aScreening Tool

The NSEQ described herein may be used either directly or in thedevelopment of tools for the detection and isolation of expressionproducts (mRNA, mRNA precursor, hnRNA, etc.), of genomic DNA or ofsynthetic products (cDNA, PCR fragments, vectors comprising NSEQ etc.).NSEQs may also be used to prepare suitable tools for detecting anencoded polypeptide or protein. NSEQ may thus be used to provide anencoded polypeptide and to generate an antibody specific for thepolypeptide.

Those skilled in the art will also recognize that short oligonucleotidessequences may be prepared based on the polynucleotide sequencesdescribed herein. For example, oligonucleotides having 10 to 20nucleotides or more may be prepared for specifically hybridizing to aNSEQ having a substantially complementary sequence and to allowdetection, identification and isolation of nucleic sequences byhybridization. Probe sequences of for example, at least 10-20nucleotides may be prepared based on a sequence found in any one of SEQID NO.:1 to 49, 50 or 169 and more particularly selected from regionsthat lack homology to undesirable sequences. Probe sequences of 20 ormore nucleotides that lack such homology may show an increasedspecificity toward the target sequence. Useful hybridization conditionsfor probes and primers are readily determinable by those of skill in theart. Stringent hybridization conditions encompassed herewith are thosethat may allow hybridization of nucleic acids that are greater than 90%homologous but which may prevent hybridization of nucleic acids that areless than 70% homologous. The specificity of a probe may be determinedby whether it is made from a unique region, a regulatory region, or froma conserved motif. Both probe specificity and the stringency ofdiagnostic hybridization or amplification (maximal, high, intermediate,or low) reactions depend on whether or not the probe identifies exactlycomplementary sequences, allelic variants, or related sequences. Probesdesigned to detect related sequences may have, for example, at least 50%sequence identity to any of the selected polynucleotides.

Furthermore, a probe may be labelled by any procedure known in the art,for example by incorporation of nucleotides linked to a “reportermolecule”. A “reporter molecule”, as used herein, may be a molecule thatprovides an analytically identifiable signal allowing detection of ahybridized probe. Detection may be either qualitative or quantitative.Commonly used reporter molecules include fluorophores, enzymes, biotin,chemiluminescent molecules, bioluminescent molecules, digoxigenin,avidin, streptavidin or radioisotopes. Commonly used enzymes includehorseradish peroxidase, alkaline phosphatase, glucose oxidase andβ-galactosidase, among others. Enzymes may be conjugated to avidin orstreptavidin for use with a biotinylated probe. Similarly, probes may beconjugated to avidin or streptavidin for use with a biotinylated enzyme.Incorporation of a reporter molecule into a DNA probe may be effected byany method known to the skilled artisan, for example by nicktranslation, primer extension, random oligo priming, by 3′ or 5′ endlabeling or by other means. In addition, hybridization probes includethe cloning of nucleic acid sequences into vectors for the production ofmRNA probes. Such vectors are known in the art, are commerciallyavailable, and may be used to synthesize RNA probes in vitro. Thelabelled polynucleotide sequences may be used in Southern or northernanalysis, dot blot, or other membrane-based technologies; in PCRtechnologies; and in micro arrays utilizing samples from subjects todetect altered expression. Oligonucleotides useful as probes forscreening of samples by hybridization assays or as primers foramplification may be packaged into kits. Such kits may contain theprobes or primers in a pre-measured or predetermined amount, as well asother suitably packaged reagents and materials needed for the particularhybridization or amplification protocol.

The expression of mRNAs identical or substantially identical to theNSEQs of the present invention may thus be detected and/or isolatedusing methods which are known in the art. Exemplary embodiment of suchmethods includes, for example and without limitation, hybridizationanalysis using oligonucleotide probes, reverse transcription and invitro nucleic acid amplification methods.

Such procedures may therefore, permit detection of mRNAs in ovariancells (e.g., ovarian cancer cells) or in any other cells expressing suchmRNAs. Expression of mRNA in a tissue-specific or a disease-specificmanner may be useful for defining the tissues and/or particular diseasestate. One of skill in the art may readily adapt the NSEQs for thesepurposes.

It is to be understood herein that the NSEQs may hybridize to asubstantially complementary sequence found in a test sample (e.g., cell,tissue, etc.). Additionally, a sequence substantially complementary toNSEQ (including fragments) may bind a NSEQ and substantially identicalsequences found in a test sample (e.g., cell, tissue, etc.).

Polypeptide encoded by an isolated NSEQ, polypeptide variants,polypeptide analogs or polypeptide fragments thereof are alsoencompassed herewith. The polypeptides whether in a premature, mature orfused form, may be isolated from lysed cells, or from the culturemedium, and purified to the extent needed for the intended use. One ofskill in the art may readily purify these proteins, polypeptides andpeptides by any available procedure. For example, purification may beaccomplished by salt fractionation, size exclusion chromatography, ionexchange chromatography, reverse phase chromatography, affinitychromatography and the like. Alternatively, PSEQ may be made by chemicalsynthesis.

Natural variants may be identified through hybridization screening of anucleic acid library or polypeptide library from different tissue, celltype, population, species, etc using the NSEQ and derived tools.

Use of NSEQ for Development of an Expression System

In order to express a polypeptide, a NSEQ able to encode any one of aPSEQ described herein may be inserted into an expression vector, i.e., avector that contains the elements for transcriptional and translationalcontrol of the inserted coding sequence in a particular host. Theseelements may include regulatory sequences, such as enhancers,constitutive and inducible promoters, and 5′ and 3′ un-translatedregions. Methods that are well known to those skilled in the art may beused to construct such expression vectors. These methods include invitro recombinant DNA techniques, synthetic techniques, and in vivogenetic recombination.

A variety of expression vector/host cell systems known to those of skillin the art may be utilized to express a polypeptide or RNA from NSEQ.These include, but are not limited to, microorganisms such as bacteriatransformed with recombinant bacteriophage, plasmid, or cosmid DNAexpression vectors; yeast transformed with yeast expression vectors;insect cell systems infected with baculovirus vectors; plant cellsystems transformed with viral or bacterial expression vectors; oranimal cell systems. For long-term production of recombinant proteins inmammalian systems, stable expression in cell lines may be effected. Forexample, NSEQ may be transformed into cell lines using expressionvectors that may contain viral origins of replication and/or endogenousexpression elements and a selectable or visible marker gene on the sameor on a separate vector. The invention is not to be limited by thevector or host cell employed.

Alternatively, RNA and/or polypeptide may be expressed from a vectorcomprising NSEQ using an in vitro transcription system or a coupled invitro transcription/translation system respectively.

In general, host cells that contain NSEQ and/or that express apolypeptide encoded by the NSEQ, or a portion thereof, may be identifiedby a variety of procedures known to those of skill in the art. Theseprocedures include, but are not limited to, DNA/DNA or DNA/RNAhybridizations, PCR amplification, and protein bioassay or immunoassaytechniques that include membrane, solution, or chip based technologiesfor the detection and/or quantification of nucleic acid or amino acidsequences. Immunological methods for detecting and measuring theexpression of polypeptides using either specific polyclonal ormonoclonal antibodies are known in the art. Examples of such techniquesinclude enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays(RIAs), and fluorescence activated cell sorting (FACS). Those of skillin the art may readily adapt these methodologies to the presentinvention.

Host cells comprising NSEQ may thus be cultured under conditions for thetranscription of the corresponding RNA (mRNA, siRNA, shRNA etc.) and/orthe expression of the polypeptide from cell culture. The polypeptideproduced by a cell may be secreted or may be retained intracellularlydepending on the sequence and/or the vector used. As will be understoodby those of skill in the art, expression vectors containing NSEQ may bedesigned to contain signal sequences that direct secretion of thepolypeptide through a prokaryotic or eukaryotic cell membrane. Due tothe inherent degeneracy of the genetic code, other DNA sequences thatencode the same, substantially the same or a functionally equivalentamino acid sequence may be produced and used, for example, to express apolypeptide encoded by NSEQ. The nucleotide sequences of the presentinvention may be engineered using methods generally known in the art inorder to alter the nucleotide sequences for a variety of purposesincluding, but not limited to, modification of the cloning, processing,and/or expression of the gene product. DNA shuffling by randomfragmentation and PCR reassembly of gene fragments and syntheticoligonucleotides may be used to engineer the nucleotide sequences. Forexample, oligonucleotide-mediated site-directed mutagenesis may be usedto introduce mutations that create new restriction sites, alterglycosylation patterns, change codon preference, produce splicevariants, and so forth. In addition, a host cell strain may be chosenfor its ability to modulate expression of the inserted sequences or toprocess the expressed polypeptide in the desired fashion. Suchmodifications of the polypeptide include, but are not limited to,acetylation, carboxylation, glycosylation, phosphorylation, lipidation,and acylation. Post-translational processing, which cleaves a “prepro”form of the polypeptide, may also be used to specify protein targeting,folding, and/or activity. Different host cells that have specificcellular machinery and characteristic mechanisms for post-translationalactivities (e.g., CHO, HeLa, MDCK, HEK293, and W138) are availablecommercially and from the American Type Culture Collection (ATCC) andmay be chosen to ensure the correct modification and processing of theexpressed polypeptide.

Those of skill in the art will readily appreciate that natural,modified, or recombinant nucleic acid sequences may be ligated to aheterologous sequence resulting in translation of a fusion polypeptidecontaining heterologous polypeptide moieties in any of theaforementioned host systems. Such heterologous polypeptide moieties mayfacilitate purification of fusion polypeptides using commerciallyavailable affinity matrices. Such moieties include, but are not limitedto, glutathione S-transferase (GST), maltose binding protein,thioredoxin, calmodulin binding peptide, 6-His (His), FLAG, c-myc,hemaglutinin (HA), and antibody epitopes such as monoclonal antibodyepitopes.

In yet a further aspect, the present invention relates to apolynucleotide which may comprise a nucleotide sequence encoding afusion protein, the fusion protein may comprise a fusion partner fusedto a peptide fragment of a protein encoded by, or a naturally occurringallelic variant polypeptide encoded by, the polynucleotide sequencedescribed herein.

Those of skill in the art will also readily recognize that the nucleicacid and polypeptide sequences may be synthesized, in whole or in part,using chemical or enzymatic methods well known in the art. For example,peptide synthesis may be performed using various solid-phase techniquesand machines such as the ABI 431A Peptide synthesizer (PE Biosystems)may be used to automate synthesis. If desired, the amino acid sequencemay be altered during synthesis and/or combined with sequences fromother proteins to produce a variant protein.

The present invention additionally relates to a bioassay for evaluatingcompounds as potential antagonists of the polypeptide described herein,the bioassay may comprise:

-   -   a) culturing test cells in culture medium containing increasing        concentrations of at least one compound whose ability to inhibit        the action of a polypeptide described herein is sought to be        determined, wherein the test cells may contain a polynucleotide        sequence described herein (for example, in a form having        improved trans-activation transcription activity, relative to        wild-type polynucleotide, and comprising a response element        operatively linked to a reporter gene); and thereafter    -   b) monitoring in the cells the level of expression of the        product of the reporter gene (encoding a reporter molecule) as a        function of the concentration of the potential antagonist        compound in the culture medium, thereby indicating the ability        of the potential antagonist compound to inhibit activation of        the polypeptide encoded by, the polynucleotide sequence        described herein.

The present invention further relates to a bioassay for evaluatingcompounds as potential agonists for a polypeptide encoded by thepolynucleotide sequence described herein, the bioassay may comprise:

-   -   a) culturing test cells in culture medium containing increasing        concentrations of at least one compound whose ability to promote        the action of the polypeptide encoded by the polynucleotide        sequence described herein is sought to be determined, wherein        the test cells may contain a polynucleotide sequence described        herein (for example, in a form having improved trans-activation        transcription activity, relative to wild-type polynucleotide,        and comprising a response element operatively linked to a        reporter gene); and thereafter    -   b) monitoring in the cells the level of expression of the        product of the reporter gene as a function of the concentration        of the potential agonist compound in the culture medium, thereby        indicating the ability of the potential agonist compound to        promote activation of a polypeptide encoded by the        polynucleotide sequence described herein.

Use of NSEQ as a Identification Tool or as a Diagnostic Screening Tool

The skilled artisan will readily recognize that NSEQ may be used toidentify a particular cell, cell type, tissue, disease and thus may beused for diagnostic purposes to determine the absence, presence, oraltered expression (i.e. increased or decreased compared to normal) ofthe expression product of a gene. Suitable NSEQ may be for example,between 10 and 20 or longer, i.e., at least 10 nucleotides long or atleast 12 nucleotides long, or at least 15 nucleotides long up to anydesired length and may comprise, for example, RNA, DNA, branched nucleicacids, and/or peptide nucleic acids (PNAs). In one alternative, thepolynucleotides may be used to detect and quantify gene expression insamples in which expression of NSEQ is correlated with disease. Inanother alternative, NSEQ may be used to detect genetic polymorphismsassociated with a disease. These polymorphisms may be detected, forexample, in the transcript, cDNA or genomic DNA.

The invention provides for the use of at least one of the NSEQ describedherein on an array and for the use of that array in a method ofdetection of a particular cell, cell type, tissue, disease for theprognosis or diagnosis of cancer. The method may comprise hybridizingthe array with a patient sample (putatively comprising or comprising atarget polynucleotide sequence substantially complementary to a NSEQ)under conditions to allow complex formation (between NSEQ and targetpolynucleotide), detecting complex formation, wherein the complexformation is indicative of the presence of the polynucleotide andwherein the absence of complex formation is indicative of the absence ofthe polynucleotide in the patient sample. The presence or absence of thepolynucleotide may be indicative of cancer such as, for example, ovariancancer or other cancer as indicated herein.

The method may also comprise the step of quantitatively or qualitativelycomparing (e.g., with a computer system, apparatus) the level of complexformation in the patient sample to that of standards for normal cells orindividual or other type, origin or grade of cancer.

The present invention provides one or more compartmentalized kits fordetection of a polynucleotide and/or polypeptide for the diagnosis orprognosis of ovarian cancer. A first kit may have a receptaclecontaining at least one isolated NSEQ or probe comprising NSEQ. Such aprobe may bind to a nucleic acid fragment which is present/absent innormal cells but which is absent/present in affected or diseased cells.Such a probe may be specific for a nucleic acid site that is normallyactive/inactive but which may be inactive/active in certain cell types.Similarly, such a probe may be specific for a nucleic acid site that maybe abnormally expressed in certain cell types. Finally, such a probe mayidentify a specific mutation. The probe may be capable of hybridizing tothe nucleic acid sequence which is mutated (not identical to the normalnucleic acid sequence), or may be capable of hybridizing to nucleic acidsequences adjacent to the mutated nucleic acid sequences. The probesprovided in the present kits may have a covalently attached reportermolecule. Probes and reporter molecules may be readily prepared asdescribed above by those of skill in the art.

Antibodies (e.g., isolated antibody) that may specifically bind to aprotein or polypeptide described herein (a PSEQ) as well as nucleicacids encoding such antibodies are also encompassed by the presentinvention.

As used herein the term “antibody” means a monoclonal antibody, apolyclonal antibody, a single chain antibody, a chimeric antibody, ahumanized antibody, a deimmunized antibody, an antigen-binding fragment,an Fab fragment; an F(ab′)₂ fragment, and Fv fragment; CDRs, or asingle-chain antibody comprising an antigen-binding fragment (e.g., asingle chain Fv).

The antibody may originate for example, from a mouse, rat or any othermammal or from other sources such as through recombinant DNAtechnologies.

The antibody may also be a human antibody which may be obtained, forexample, from a transgenic non-human mammal capable of expressing humanIg genes. The antibody may also be a humanised antibody which maycomprise, for example, one or more complementarity determining regionsof non-human origin. It may also comprise a surface residue of a humanantibody and/or framework regions of a human antibody. The antibody mayalso be a chimeric antibody which may comprise, for example, variabledomains of a non-human antibody and constant domains of a humanantibody.

The antibody of the present invention may be mutated and selected basedon an increased affinity, solubility, stability, specificity and/or forone of a polypeptide described herein and/or based on a reducedimmunogenicity in a desired host or for other desirable characteristics.

Suitable antibodies may bind to unique antigenic regions or epitopes inthe polypeptides, or a portion thereof. Epitopes and antigenic regionsuseful for generating antibodies may be found within the proteins,polypeptides or peptides by procedures available to one of skill in theart. For example, short, unique peptide sequences may be identified inthe proteins and polypeptides that have little or no homology to knownamino acid sequences. Preferably the region of a protein selected to actas a peptide epitope or antigen is not entirely hydrophobic; hydrophilicregions are preferred because those regions likely constitute surfaceepitopes rather than internal regions of the proteins and polypeptides.These surface epitopes are more readily detected in samples tested forthe presence of the proteins and polypeptides. Such antibodies mayinclude, but are not limited to, polyclonal, monoclonal, chimeric, andsingle chain antibodies, Fab fragments, and fragments produced by a Fabexpression library. The production of antibodies is well known to one ofskill in the art and is not intended to be limited herein.

Peptides may be made by any procedure known to one of skill in the art,for example, by using in vitro translation or chemical synthesisprocedures or by introducing a suitable expression vector into cells.Short peptides which provide an antigenic epitope but which bythemselves are too small to induce an immune response may be conjugatedto a suitable carrier. Suitable carriers and methods of linkage are wellknown in the art. Suitable carriers are typically large macromoleculessuch as proteins, polysaccharides and polymeric amino acids. Examplesinclude serum albumins, keyhole limpet hemocyanin, ovalbumin, polylysineand the like. One of skill in the art may use available procedures andcoupling reagents to link the desired peptide epitope to such a carrier.For example, coupling reagents may be used to form disulfide linkages orthioether linkages from the carrier to the peptide of interest. If thepeptide lacks a disulfide group, one may be provided by the addition ofa cysteine residue. Alternatively, coupling may be accomplished byactivation of carboxyl groups.

The minimum size of peptides useful for obtaining antigen specificantibodies may vary widely. The minimum size must be sufficient toprovide an antigenic epitope that is specific to the protein orpolypeptide. The maximum size is not critical unless it is desired toobtain antibodies to one particular epitope. For example, a largepolypeptide may comprise multiple epitopes, one epitope beingparticularly useful and a second epitope being immunodominant, etc.Typically, antigenic peptides selected from the present proteins andpolypeptides will range without limitation, from 5 to about 100 aminoacids in length. More typically, however, such an antigenic peptide willbe a maximum of about 50 amino acids in length, and preferably a maximumof about 30 amino acids. It is usually desirable to select a sequence ofabout 6, 8, 10, 12 or 15 amino acids, up to about 20 or 25 amino acids(and any number therebetween).

Amino acid sequences comprising useful epitopes may be identified in anumber of ways. For example, preparing a series of short peptides thattaken together span the entire protein sequence may be used to screenthe entire protein sequence. One of skill in the art may routinely testa few large polypeptides for the presence of an epitope showing adesired reactivity and also test progressively smaller and overlappingfragments to identify a preferred epitope with the desired specificityand reactivity.

As mentioned herein, antigenic polypeptides and peptides are useful forthe production of monoclonal and polyclonal antibodies. Antibodies to apolypeptide encoded by the polynucleotides of NSEQ, polypeptide analogsor portions thereof, may be generated using methods that are well knownin the art. For example, monoclonal antibodies may be prepared using anytechnique that provides for the production of antibody molecules bycontinuous cell lines in culture. These include, but are not limited to,the hybridoma, the human B-cell hybridoma, and the EBV-hybridomatechniques. In addition, techniques developed for the production ofchimeric antibodies may be used. Alternatively, techniques described forthe production of single chain antibodies may be employed. Fabs that maycontain specific binding sites for a polypeptide encoded by thepolynucleotides of NSEQ, or a portion thereof, may also be generated.Various immunoassays may be used to identify antibodies having thedesired specificity. Numerous protocols for competitive binding orimmunoradiometric assays using either polyclonal or monoclonalantibodies with established specificities are well known in the art.

To obtain polyclonal antibodies, a selected animal may be immunized witha protein or polypeptide. Serum from the animal may be collected andtreated according to known procedures. Polyclonal antibodies to theprotein or polypeptide of interest may then be purified by affinitychromatography. Techniques for producing polyclonal antisera are wellknown in the art.

Monoclonal antibodies (MAbs) may be made by one of several proceduresavailable to one of skill in the art, for example, by fusing antibodyproducing cells with immortalized cells and thereby making a hybridoma.The general methodology for fusion of antibody producing B cells to animmortal cell line is well within the province of one skilled in theart. Another example is the generation of MAbs from mRNA extracted frombone marrow and spleen cells of immunized animals using combinatorialantibody library technology.

One drawback of MAbs derived from animals or from derived cell lines isthat although they may be administered to a patient for diagnostic ortherapeutic purposes, they are often recognized as foreign antigens bythe immune system and are unsuitable for continued use. Antibodies thatare not recognized as foreign antigens by the human immune system havegreater potential for both diagnosis and treatment. Methods forgenerating human and humanized antibodies are now well known in the art.

Chimeric antibodies may be constructed in which regions of a non-humanMAb are replaced by their human counterparts. A preferred chimericantibody is one that has amino acid sequences that comprise one or morecomplementarity determining regions (CDRs) of a non-human Mab that bindsto a polypeptide encoded by the polynucleotides of NSEQ, or a portionthereof, grafted to human framework (FW) regions. Methods for producingsuch antibodies are well known in the art. Amino acid residuescorresponding to CDRs and FWs are known to one of average skill in theart.

A variety of methods have been developed to preserve or to enhanceaffinity for antigen of antibodies comprising grafted CDRs. One way isto include in the chimeric antibody the foreign framework residues thatinfluence the conformation of the CDR regions. A second way is to graftthe foreign CDRs onto human variable domains with the closest homologyto the foreign variable region. Thus, grafting of one or more non-humanCDRs onto a human antibody may also involve the substitution of aminoacid residues which are adjacent to a particular CDR sequence or whichare not contiguous with the CDR sequence but which are packed againstthe CDR in the overall antibody variable domain structure and whichaffect the conformation of the CDR. Humanized antibodies of theinvention therefore include human antibodies which comprise one or morenon-human CDRs as well as such antibodies in which additionalsubstitutions or replacements have been made to preserve or enhancebinding characteristics.

Chimeric antibodies of the invention also include antibodies that havebeen humanized by replacing surface-exposed residues to make the MAbappear human. Because the internal packing of amino acid residues in thevicinity of the antigen-binding site remains unchanged, affinity ispreserved. Substitution of surface-exposed residues of a polypeptideencoded by the polynucleotides of NSEQ (or a portion thereof)-antibodyaccording to the invention for the purpose of humanization does not meansubstitution of CDR residues or adjacent residues that influenceaffinity for a polypeptide encoded by the polynucleotides of NSEQ, or aportion thereof.

Chimeric antibodies may also include antibodies where some or allnon-human constant domains have been replaced with human counterparts.This approach has the advantage that the antigen-binding site remainsunaffected. However, significant amounts of non-human sequences may bepresent where variable domains are derived entirely from non-humanantibodies.

Antibodies of the invention include human antibodies that are antibodiesconsisting essentially of human sequences. Human antibodies may beobtained from phage display libraries wherein combinations of humanheavy and light chain variable domains are displayed on the surface offilamentous phage. Combinations of variable domains are typicallydisplayed on filamentous phage in the form of Fab's or scFvs. Thelibrary may be screened for phage bearing combinations of variabledomains having desired antigen-binding characteristics. Preferredvariable domain combinations are characterized by high affinity for apolypeptide encoded by the polynucleotides of NSEQ, or a portionthereof. Preferred variable domain combinations may also becharacterized by high specificity for a polypeptide encoded by thepolynucleotides of NSEQ, or a portion thereof, and littlecross-reactivity to other related antigens. By screening from very largerepertoires of antibody fragments, (2-10×10¹⁰) a good diversity of highaffinity Mabs may be isolated, with many expected to have sub-nanomolaraffinities for a polypeptide encoded by the polynucleotides of NSEQ, ora portion thereof.

Antibodies of the invention may include complete anti-polypeptideantibodies as well as antibody fragments and derivatives that comprise abinding site for a polypeptide encoded by the polynucleotides of NSEQ,or a portion thereof. Derivatives are macromolecules that comprise abinding site linked to a functional domain. Functional domains mayinclude, but are not limited to signalling domains, toxins, enzymes andcytokines.

Alternatively, human antibodies may be obtained from transgenic animalsinto which un-rearranged human Ig gene segments have been introduced andin which the endogenous mouse Ig genes have been inactivated. Preferredtransgenic animals contain very large contiguous Ig gene fragments thatare over 1 Mb in size but human polypeptide-specific Mabs of moderateaffinity may be raised from transgenic animals containing smaller geneloci. Transgenic animals capable of expressing only human Ig genes mayalso be used to raise polyclonal antiserum comprising antibodies solelyof human origin.

Antibodies of the invention may include those for which bindingcharacteristics have been improved by direct mutation or by methods ofaffinity maturation. Affinity and specificity may be modified orimproved by mutating CDRs and screening for antigen binding sites havingthe desired characteristics. CDRs may be mutated in a variety of ways.One way is to randomize individual residues or combinations of residuesso that in a population of otherwise identical antigen binding sites,all twenty amino acids may be found at particular positions.Alternatively, mutations may be induced over a range of CDR residues byerror prone PCR methods. Phage display vectors containing heavy andlight chain variable region gene may be propagated in mutator strains ofE. coli. These methods of mutagenesis are illustrative of the manymethods known to one of skill in the art.

The antibody may further comprise a detectable label (reporter molecule)attached thereto.

There is provided also methods of producing antibodies able tospecifically bind to one of a polypeptide, polypeptide fragments, orpolypeptide analogs described herein, the method may comprise:

-   -   a) immunizing a mammal (e.g., mouse, a transgenic mammal capable        of producing human Ig, etc.) with a suitable amount of a PSEQ        described herein including, for example, a polypeptide fragment        comprising at least 6 (e.g., 8, 10, 12 etc.) consecutive amino        acids of a PSEQ;    -   b) collecting the serum from the mammal; and    -   c) isolating the polypeptide-specific antibodies from the serum        of the mammal.

The method may further comprise the step of administering a second doseto the mammal (e.g., animal).

Methods of producing a hybridoma which secretes an antibody thatspecifically binds to a polypeptide are also encompassed herewith andare known in the art.

The method may comprise:

-   -   a) immunizing a mammal (e.g., mouse, a transgenic mammal capable        of producing human Ig, etc.) with a suitable amount of a PSEQ        thereof;    -   b) obtaining lymphoid cells from the immunized animal obtained        from (a);    -   c) fusing the lymphoid cells with an immortalizing cell to        produce hybrid cells; and    -   d) selecting hybrid cells which produce antibody that        specifically binds to a PSEQ thereof.

Also encompassed by the present invention is a method of producing anantibody that specifically binds to one of the polypeptide describedherein, the method may comprise:

-   -   a) synthesizing a library of antibodies (e.g., antigen binding        fragment) on phage or ribosomes;    -   b) panning the library against a sample by bringing the phage or        ribosomes into contact with a composition comprising a        polypeptide or polypeptide fragment described herein;    -   c) isolating phage which binds to the polypeptide or polypeptide        fragment, and;    -   d) obtaining an antibody from the phage or ribosomes.

The antibody of the present invention may thus be obtained, for example,from a library (e.g., bacteriophage library) which may be prepared, forexample, by

-   -   a) extracting cells which are responsible for production of        antibodies from a host mammal;    -   b) isolating RNA from the cells of (a);    -   c) reverse transcribing mRNA to produce cDNA;    -   d) amplifying the cDNA using a (antibody-specific) primer; and    -   e) inserting the cDNA of (d) into a phage display vector or        ribosome display cassette such that antibodies are expressed on        the phage or ribosomes.

In order to generate antibodies, the host animal may be immunized withpolypeptide and/or a polypeptide fragment and/or analog described hereinto induce an immune response prior to extracting the cells which areresponsible for production of antibodies.

The antibodies obtained by the means described herein may be useful fordetecting proteins, variant and derivative polypeptides in specifictissues or in body fluids. Moreover, detection of aberrantly expressedproteins or protein fragments is probative of a disease state. Forexample, expression of the present polypeptides encoded by thepolynucleotides of NSEQ, or a portion thereof, may indicate that theprotein is being expressed at an inappropriate rate or at aninappropriate developmental stage. Hence, the present antibodies may beuseful for detecting diseases associated with protein expression fromNSEQs disclosed herein.

For in vivo detection purposes, antibodies may be those which preferablyrecognize an epitope present at the surface of a tumor cell.

A variety of protocols for measuring polypeptides, including ELISAs,RIAs, and FACS, are well known in the art and provide a basis fordiagnosing altered or abnormal levels of expression. Standard values forpolypeptide expression are established by combining samples taken fromhealthy subjects, preferably human, with antibody to the polypeptideunder conditions for complex formation. The amount of complex formationmay be quantified by various methods, such as photometric means.Quantities of polypeptide expressed in disease samples may be comparedwith standard values. Deviation between standard and subject values mayestablish the parameters for diagnosing or monitoring disease.

Design of immunoassays is subject to a great deal of variation and avariety of these are known in the art. Immunoassays may use a monoclonalor polyclonal antibody reagent that is directed against one epitope ofthe antigen being assayed. Alternatively, a combination of monoclonal orpolyclonal antibodies may be used which are directed against more thanone epitope. Protocols may be based, for example, upon competition whereone may use competitive drug screening assays in which neutralizingantibodies capable of binding a polypeptide encoded by thepolynucleotides of NSEQ, or a portion thereof, specifically compete witha test compound for binding the polypeptide. Alternatively one may use,direct antigen-antibody reactions or sandwich type assays and protocolsmay, for example, make use of solid supports or immunoprecipitation.Furthermore, antibodies may be labelled with a reporter molecule foreasy detection. Assays that amplify the signal from a bound reagent arealso known. Examples include immunoassays that utilize avidin andbiotin, or which utilize enzyme-labelled antibody or antigen conjugates,such as ELISA assays.

Kits suitable for immunodiagnosis and containing the appropriatelabelled reagents include antibodies directed against the polypeptideprotein epitopes or antigenic regions, packaged appropriately with theremaining reagents and materials required for the conduct of the assay,as well as a suitable set of assay instructions.

The present invention therefore provides a kit for specificallydetecting a polypeptide described herein, the kit may comprise, forexample, an antibody or antibody fragment capable of bindingspecifically to the polypeptide described herein.

In accordance with the present invention, the kit may be a diagnostickit, which may comprise:

-   -   a) one or more antibodies described herein; and    -   b) a detection reagent which may comprise a reporter group.

In accordance with the present invention, the antibodies may beimmobilized on a solid support. The detection reagent may comprise, forexample, an anti-immunoglobulin, protein G, protein A or lectin etc. Thereporter group may be selected, without limitation, from the groupconsisting of radioisotopes, fluorescent groups, luminescent groups,enzymes, biotin and dye particles

Use of NSEQ, PSEQ as a Therapeutic or Therapeutic Targets

One of skill in the art will readily appreciate that the NSEQ, PSEQ,expression systems, assays, kits and array discussed above may also beused to evaluate the efficacy of a particular therapeutic treatmentregimen, in animal studies, in clinical trials, or to monitor thetreatment of an individual subject. Once the presence of disease isestablished and a treatment protocol is initiated, hybridization oramplification assays may be repeated on a regular basis to determine ifthe level of mRNA or protein in the patient (patient's blood, tissue,cell etc.) begins to approximate the level observed in a healthysubject. The results obtained from successive assays may be used to showthe efficacy of treatment over a period ranging from several days tomany years.

In yet another aspect of the invention, NSEQ may be used therapeuticallyfor the purpose of expressing mRNA and polypeptide, or conversely toblock transcription and/or translation of the mRNA. Expression vectorsmay be constructed using elements from retroviruses, adenoviruses,herpes or vaccinia viruses, or bacterial plasmids, and the like. Thesevectors may be used for delivery of nucleotide sequences to a particulartarget organ, tissue, or cell population. Methods well known to thoseskilled in the art may be used to construct vectors to express nucleicacid sequences or their complements.

Alternatively, NSEQ may be used for somatic cell or stem cell genetherapy. Vectors may be introduced in vivo, in vitro, and ex vivo. Forex vivo therapy, vectors are introduced into stem cells taken from thesubject, and the resulting transgenic cells are clonally propagated forautologous transplant back into that same subject. Delivery of NSEQ bytransfection, liposome injections, or polycationic amino polymers may beachieved using methods that are well known in the art. Additionally,endogenous NSEQ expression may be inactivated using homologousrecombination methods that insert an inactive gene sequence into thecoding region or other targeted region of NSEQ.

Depending on the specific goal to be achieved, vectors containing NSEQmay be introduced into a cell or tissue to express a missing polypeptideor to replace a non-functional polypeptide. Of course, when one wishesto express PSEQ in a cell or tissue, one may use a NSEQ able to encodesuch PSEQ for that purpose or may directly administer PSEQ to that cellor tissue.

On the other hand, when one wishes to attenuate or inhibit theexpression of PSEQ, one may use a NSEQ (e.g., an inhibitory NSEQ) whichis substantially complementary to at least a portion of a NSEQ able toencode such PSEQ.

The expression of an inhibitory NSEQ may be done by cloning theinhibitory NSEQ into a vector and introducing the vector into a cell todown-regulate the expression of a polypeptide encoded by the targetNSEQ. Complementary or anti-sense sequences may also comprise anoligonucleotide derived from the transcription initiation site;nucleotides between about positions −10 and +10 from the ATG may beused. Therefore, inhibitory NSEQ may encompass a portion which issubstantially complementary to a desired nucleic acid molecule to beinhibited and a portion (sequence) which binds to an untranslatedportion of the nucleic acid.

Similarly, inhibition may be achieved using triple helix base-pairingmethodology. Triple helix pairing is useful because it causes inhibitionof the ability of the double helix to open sufficiently for the bindingof polymerases, transcription factors, or regulatory molecules. Recenttherapeutic advances using triplex DNA have been described in theliterature. (See, e.g., Gee et al. 1994)

Ribozymes, enzymatic RNA molecules, may also be used to catalyze thecleavage of mRNA and decrease the levels of particular mRNAs, such asthose comprising the polynucleotide sequences of the invention.Ribozymes may cleave mRNA at specific cleavage sites. Alternatively,ribozymes may cleave mRNAs at locations dictated by flanking regionsthat form complementary base pairs with the target mRNA. Theconstruction and production of ribozymes is well known in the art.

RNA molecules may be modified to increase intracellular stability andhalf-life. Possible modifications include, but are not limited to, theaddition of flanking sequences at the 5′ and/or 3′ ends of the molecule,or the use of phosphorothioate or 2′ O-methyl rather than phosphodiesterlinkages within the backbone of the molecule. Alternatively,nontraditional bases such as inosine, queosine, and wybutosine, as wellas acetyl-, methyl-, thio-, and similarly modified forms of adenine,cytidine, guanine, thymine, and uridine which are not as easilyrecognized by endogenous endonucleases, may be included.

Pharmaceutical compositions are also encompassed by the presentinvention. The pharmaceutical composition may comprise at least one NSEQor PSEQ and a pharmaceutically acceptable carrier.

As it will be appreciated form those of skill in the art, thespecificity of expression NSEQ and/or PSEQ in tumor cells mayadvantageously be used for inducing an immune response (through theiradministration) in an individual having, or suspected of having a tumorexpressing such sequence. Administration of NSEQ and/or PSEQ inindividuals at risk of developing a tumor expressing such sequence isalso encompassed herewith.

In addition to the active ingredients, a pharmaceutical composition maycontain pharmaceutically acceptable carriers comprising excipients andauxiliaries that facilitate processing of the active compounds intopreparations that may be used pharmaceutically.

For any compound, the therapeutically effective dose may be estimatedinitially either in cell culture assays or in animal models such asmice, rats, rabbits, dogs, or pigs. An animal model may also be used todetermine the concentration range and route of administration. Suchinformation may then be used to determine useful doses and routes foradministration in humans. These techniques are well known to one skilledin the art and a therapeutically effective dose refers to that amount ofactive ingredient that ameliorates the symptoms or condition.Therapeutic efficacy and toxicity may be determined by standardpharmaceutical procedures in cell cultures or with experimental animals,such as by calculating and contrasting the ED₅₀ (the dosetherapeutically effective in 50% of the population) and LD₅₀ (the doselethal to 50% of the population) statistics. Any of the therapeuticcompositions described above may be applied to any subject in need ofsuch therapy, including, but not limited to, mammals such as dogs, cats,cows, horses, rabbits, monkeys, and most preferably, humans.

The pharmaceutical compositions utilized in this invention may beadministered by any number of routes including, but not limited to,oral, intravenous, intramuscular, intra-arterial, intramedullary,intrathecal, intraventricular, transdermal, subcutaneous,intraperitoneal, intranasal, enteral, topical, sublingual, or rectalmeans.

The term “treatment” for purposes of this disclosure refers to boththerapeutic treatment and prophylactic or preventative measures, whereinthe object is to prevent or slow down (lessen) the targeted pathologiccondition or disorder. Those in need of treatment include those alreadywith the disorder as well as those prone to have the disorder or thosein whom the disorder is to be prevented.

Use of NSEQ in General Research

The invention also provides products, compositions, processes andmethods that utilize a NSEQ described herein, a polypeptide encoded by aNSEQ described herein, a PSEQ described herein for research, biological,clinical and therapeutic purposes. For example, to identify splicevariants, mutations, and polymorphisms and to generate diagnostic andprognostic tools.

NSEQ may be extended utilizing a partial nucleotide sequence andemploying various PCR-based methods known in the art to detect upstreamsequences such as promoters and other regulatory elements. Additionally,one may use an XL-PCR kit (PE Biosystems, Foster City Calif.), nestedprimers, and commercially available cDNA libraries (Life Technologies,Rockville Md.) or genomic libraries (Clontech, Palo Alto Calif.) toextend the sequence.

The polynucleotides (NSEQ) may also be used as targets in a microarray.The microarray may be used to monitor the expression patterns of largenumbers of genes simultaneously and to identify splice variants,mutations, and polymorphisms. Information derived from analyses of theexpression patterns may be used to determine gene function, to identifya particular cell, cell type or tissue, to understand the genetic basisof a disease, to diagnose a disease, and to develop and monitor theactivities of therapeutic agents used to treat a disease. Microarraysmay also be used to detect genetic diversity, single nucleotidepolymorphisms which may characterize a particular population, at thegenomic level.

The polynucleotides (NSEQ) may also be used to generate hybridizationprobes useful in mapping the naturally occurring genomic sequence.Fluorescent in situ hybridization (FISH) may be correlated with otherphysical chromosome mapping techniques and genetic map data.

It is to be understood herein that a sequence which is upregulated in anovarian cancer cell (e.g., malignant ovarian cancer cell) may representa sequence which is involved in or responsible for the growth,development, maligancy and so on, of the cancer cell (referred herein asa positive regulator of ovarian cancer). It is also to be understoodthat a sequence which is downregulated (unexpressed or expressed at lowlevels) in a malignant ovarian cancer cell may represent a sequencewhich is responsible for the maintenance of the normal status(untransformed) of an ovarian cell (referred herein as a negativeregulator of ovarian cancer). Therefore, both the presence or absence ofsome sequences may be indicative of the disease or may be indicative ofthe disease, probability of having a disease, degree of severity of thedisease (staging).

Therefore, the present invention relates in an aspect thereof to anisolated polynucleotide (e.g., exogenous form of) which may comprise amember selected from the group consisting of;

-   -   a) a polynucleotide which may comprise or consist of any one of        SEQ ID NO.:1 to SEQ ID NO. 49 and SEQ ID NO. 169,    -   b) a polynucleotide which may comprise the open reading frame of        any one of SEQ ID NO.:1 to SEQ ID NO. 49 and SEQ ID NO. 169,    -   c) a polynucleotide which may comprise a transcribed or        transcribable portion of any one of SEQ. ID. NOs:1 to 49 and        169, which may be, for example, free of untranslated or        untranslatable portion(s),    -   d) a polynucleotide which may comprise a translated or        translatable portion of any one of SEQ. ID. NOs:1 to 49 and 169        (e.g., coding portion),    -   e) a polynucleotide which may comprise a sequence substantially        identical (e.g., from about 50 to 100%, or about 60 to 100% or        about 70 to 100% or about 80 to 100% or about 85, 90, 95 to 100%        identical over the entire sequence or portion of sequences) to        a), b), c), or d);    -   f) a polynucleotide which may comprise a sequence substantially        complementary (e.g., from about 50 to 100%, or about 60 to 100%        or about 70 to 100% or about 80 to 100% or about 85, 90, 95 to        100% complementarity over the entire sequence or portion of        sequences) to a), b), c), or d) and;    -   g) a fragment of any one of a) to f) including polynucleotides        which consist in the above.

More specifically, the present invention relates to expressedpolynucleotides which are selected from the group consisting of;

-   -   a) a polynucleotide which may comprise or consist of any one of        SEQ ID NO.: 1, SEQ ID NO.:14, SEQ ID NO.:16, SEQ ID NO.:19, SEQ        ID NO.:20, SEQ ID NO.:22, SEQ ID NO.:28, SEQ ID NO.:37, SEQ ID        NO.:41, SEQ ID NO.:45, SEQ ID NO.:46, SEQ ID NO.:47 and SEQ ID        NO.:49 and even more specifically those which are selected from        the group consisting of SEQ ID NO.: 14, SEQ ID NO.:19, SEQ ID        NO.: 22, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID        NO.:46 and SEQ ID NO.:49,    -   b) a polynucleotide which may comprise the open reading frame of        any one of SEQ ID NO.: 1, SEQ ID NO.:14, SEQ ID NO.:16, SEQ ID        NO.:19, SEQ ID NO.:20, SEQ ID NO.:22, SEQ ID NO.:28, SEQ ID        NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46, SEQ ID        NO.:47 and SEQ ID NO.:49 and even more specifically those which        are selected from the group consisting of SEQ ID NO.: 14, SEQ ID        NO.:19, SEQ ID NO.: 22, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID        NO.:45, SEQ ID NO.:46 and SEQ ID NO.:49,    -   c) a polynucleotide which may comprise a transcribed or        transcribable portion of any one of SEQ ID NO.: 1, SEQ ID        NO.:14, SEQ ID NO.:16, SEQ ID NO.:19, SEQ ID NO.:20, SEQ ID        NO.:22, SEQ ID NO.:28, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID        NO.:45, SEQ ID NO.:46, SEQ ID NO.:47 and SEQ ID NO.:49 and even        more specifically those which are selected from the group        consisting of SEQ ID NO.: 14, SEQ ID NO.:19, SEQ ID NO.: 22, SEQ        ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46 and SEQ        ID NO.:49, which may be, for example, free of untranslated or        untranslatable portion(s),    -   d) a polynucleotide which may comprise a translated or        translatable portion of any one of SEQ ID NO.: 1, SEQ ID NO.:14,        SEQ ID NO.:16, SEQ ID NO.:19, SEQ ID NO.:20, SEQ ID NO.:22, SEQ        ID NO.:28, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID        NO.:46, SEQ ID NO.:47 and SEQ ID NO.:49 and even more        specifically those which are selected from the group consisting        of SEQ ID NO.: 14, SEQ ID NO.:19, SEQ ID NO.: 22, SEQ ID NO.:37,        SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46 and SEQ ID NO.:49,        (e.g., coding portion),    -   e) a polynucleotide which may comprise a sequence substantially        identical (e.g., from about 50 to 100%, or about 60 to 100% or        about 70 to 100% or about 80 to 100% or about 85, 90, 95 to 100%        identical over the entire sequence or portion of sequences) to        a), b), c), or d);    -   f) a polynucleotide which may comprise a sequence substantially        complementary (e.g., from about 50 to 100%, or about 60 to 100%        or about 70 to 100% or about 80 to 100% or about 85, 90, 95 to        100% complementarity over the entire sequence or portion of        sequences) to a), b), c), or d) and;    -   g) a fragment of any one of a) to f)        including polynucleotides which consist in the above.

Vectors (e.g., a viral vector, a mammalian vector, a plasmid, a cosmid,etc.) which may comprise the polynucleotides described herein are alsoencompassed by the present invention. The vector may be, for example, anexpression vector.

The present invention also provides a library of polynucleotidecomprising at least one polynucleotide (e.g., at least two, etc.)described herein (may include SEQ ID NO.:50). The library may be, forexample, an expression library. Some or all of the polynucleotidesdescribed herein may be contained within an expression vector. Thepresent invention also relates to a polypeptide library which maycomprise at least one (e.g., at least two, etc.) polypeptide asdescribed herein.

In another aspect, the present invention provides arrays which maycomprise at least one polynucleotide (e.g., at least two, etc.)described herein. The present invention also provides an isolated cell(e.g., an isolated live cell such as an isolated mammalian cell, abacterial cell, a yeast cell, an insect cell, etc.) which may comprisethe polynucleotide, the vector or the polypeptide described herein.

In yet a further aspect the present invention relates to a compositioncomprising the polynucleotide and/or polypeptide described herein.

In accordance with the present invention, the composition may be, forexample, a pharmaceutical composition which may comprise apolynucleotide and/or a polypeptide described herein and apharmaceutically acceptable carrier. More specifically, thepharmaceutical composition may be used for the treatment of ovariancancer and/or for inhibiting the growth of an ovarian cancer cell.

Polynucleotides fragments of those listed above includes polynucleotidescomprising at least 10 nucleic acids which may be identical to acorresponding portion of any one of a) to e) and more particularly acoding portion of any one of SEQ ID NO.:1 to 49, 50 or 169.

Another exemplary embodiment of polynucleotide fragments encompassed bythe present invention includes polynucleotides comprising at least 10nucleic acids which may be substantially complementary to acorresponding portion of a coding portion of any one of SEQ ID NO.:1 to49, 50 or 169 and encompasses, for example, fragments selected from thegroup consisting of any one of SEQ ID NO.: 103 to 150.

These above sequences may represent powerful markers of cancer and moreparticularly of, ovarian cancer, breast cancer, prostate cancer,leukemia, melanoma, renal cancer, colon cancer, lung cancer, cancer ofthe central nervous system and any combination thereof.

Based on the results presented herein and upon reading the presentdescription, a person skilled in the art will understand that theappearance of a positive signal upon testing (hybridization, PCRamplification etc.) for the presence of a given sequence amongst thoseexpressed in a cancer cell, indicates that such sequence is specificallyexpressed in that type of cancer cell. A person skilled in the art willalso understand that, sequences which are specifically expressed in acertain types of cancer cell may be used for developing tools for thedetection of this specific type of cancer cell and may also be used astargets in the development of anticancer drugs.

A positive signal may be in the form of a band in a gel followingelectrophoresis, Northern blot or Western blot, a PCR fragment detectedby emission of fluorescence, etc.

As it will be understood, sequences which are particularly useful forthe development of tools for the detection of cancer cell may preferablybe expressed at lower levels in at least some normal cells(non-cancerous cells).

For example, in FIG. 57 and related description, the appearance of aband upon RT-PCR amplification of mRNAs obtained from ovarian cancercells, renal cancer cells, lung cancer cells, breast cancer cells andmelanoma cells indicates that SEQ ID NO.:1 is expressed in such cancercells and that SEQ ID NO.:1 may therefore represent a valid marker andtarget for these types of cancer cells. Similar conclusions may bederived from the results obtained from other Figures and relateddescription.

NSEQs chosen among those which are substantially complementary to thoselisted in Table 2, or to fragments of those of Table 2, may be used forthe treatment of cancer.

The present invention therefore relates to a method for identifying acancer cell. The method may comprise contacting a cell, a cell sample(cell lysate), a body fluid (blood, urine, plasma, saliva etc.) or atissue with a reagent which may be, for example, capable of specificallybinding at least one NSEQ or PSEQ described herein. The method may moreparticularly comprise contacting a sequence isolated or derived suchcell, sample, fluid or tissue. The complex formed may be detected usingmethods known in the art.

In accordance with the present invention, the presence of the abovementioned complex may be indicative (a positive indication of thepresence) of the presence of a cancer cell.

The present invention also relates in an additional aspect thereof to amethod for the diagnosis or prognosis of cancer. The method maycomprise, for example, detecting, in a cell, tissue, sample, body fluid,etc., at least one NSEQ or PSEQ described herein.

The cell, cell sample, body fluid or tissue may originate, for example,from an individual which has or is suspected of having a cancer and moreparticularly ovarian cancer, breast cancer, prostate cancer, leukemia,melanoma, renal cancer, colon cancer, lung cancer and/or cancer of thecentral nervous system Any of the above mentioned methods may furthercomprise comparing the level obtained with at least one reference levelor value.

Detection of NSEQ may require an amplification (e.g., PCR) step in orderto have sufficient material for detection purposes.

In accordance with the present invention, the polynucleotide describedherein may comprise, for example, a RNA molecule, a DNA molecule,including those which are partial or complete, single-stranded ordouble-stranded, hybrids, modified by a group etc.

Other aspects of the present invention which are encompassed herewithcomprises the use of at least one NSEQ or PSEQ described herein andderived antibodies in the manufacture of a composition foridentification or detection of a cancer cell (e.g., a tumor cell) or forinhibiting or lowering the growth of cancer cell (e.g., for treatment ofovarian cancer or other cancer).

As some NSEQ and PSEQ are expressed at higher levels in malignantovarian cancer than in LMP detection of such NSEQ or PSEQ in a samplefrom an individual (or in vivo) one may rule-out a low malignantpotential ovarian cancer and may therefore conclude in a diagnostic of amalignant ovarian cancer. Furthermore, detection of the NSEQ or PSEQ ina cell, tissue, sample or body fluid from an individual may also beindicative of a late-stage malignant ovarian cancer. As such, therapiesadapted for the treatment of a malignant ovarian cancer or a late-stagemalignant ovarian cancer may be commenced.

In accordance with an embodiment of the present invention, the methodmay also comprise a step of qualitatively or quantitatively comparingthe level (amount, presence) of at least one complex present in the testcell, test sample, test fluid or test tissue with the level of complexin a normal cell, a normal cell sample, a normal body fluid, a normaltissue or a reference value (e.g., for a non-cancerous condition).

The normal cell may be any cell which does not substantially express thedesired sequence to be detected. Examples of such normal cells areincluded for example, in the description of the drawings section. Anormal cell sample or tissue thus include, for example, a normal(non-cancerous) ovarian cell, a normal breast cell, a normal prostatecell, a normal lymphocyte, a normal skin cell, a normal renal cell, anormal colon cell, a normal lung cell and/or a normal cell of thecentral nervous system. For comparison purposes, a normal cell may bechosen from those of identical or similar cell type.

Of course, the presence of more than one complex may be performed inorder to increase the precision of the diagnostic method. As such, atleast two complexes (e.g., formed by a first reagent and a firstpolynucleotide and a second reagent or a second polynucleotide) ormultiple complexes may be detected.

An exemplary embodiment of a reagent which may be used for detecting aNSEQ described herein is a polynucleotide which may comprise a sequencesubstantially complementary to the NSEQ.

A suitable reference level or value may be, for example, derived fromthe level of expression of a specified sequence in a low malignantpotential ovarian cancer and/or from a normal cell.

It will be understood herein that a higher level of expression measuredin a cancer cell, tissue or sample in comparison with a reference valueor sample is a indicative of the presence of cancer in the testedindividual.

For example, the higher level measured in an ovarian cell, ovariantissue or a sample of ovarian origin compared to a reference level orvalue for a normal cell (normal ovarian cell or normal non-ovarian cell)may be indicative of an ovarian cancer. For comparison purpose, thepresence or level of expression of a desired NSEQ or PSEQ to be detectedor identified may be compared with the presence, level of expression,found in a normal cell which has been shown herein not to express thedesired sequence.

Therapeutic uses and methods are also encompassed herewith.

The invention therefore provides polynucleotides which may be able tolower or inhibit the growth of an ovarian cancer cell (e.g., in a mammalor mammalian cell thereof).

The present invention therefore relates in a further aspect to the useof a polynucleotide sequence which may be selected from the groupconsisting of

-   -   a) a polynucleotide which may comprise a sequence substantially        complementary to any of SEQ ID NO.:1 to SEQ ID NO. 49, 50 or 169    -   b) a polynucleotide which may comprise a sequence substantially        complementary to a transcribed or transcribable portion of any        one of SEQ. ID. NOs:1 to 49, 50 or 169,    -   c) a polynucleotide which may comprise a sequence substantially        complementary to a translated or translatable portion of any one        of SEQ. ID. NOs:1 to 49, 50 or 169, and;    -   d) a fragment of any one of a) to c) for reducing, lowering or        inhibiting the growth of a cancer cell.

The polynucleotide may be selected, for example, from the groupconsisting of polynucleotides which may comprise a sequence of at least10 nucleotides which is complementary to the nucleic acid sequence ofany one of SEQ ID NO.: 1 to 49, 50 and 169 (to a translated portionwhich may be free, for example, of untranslated portions).

Of course, the present invention encompasses immunizing an individual byadministering a NSEQ (e.g., in an expression vector) or a PSEQ.

The present invention also relates to a method of reducing or slowingthe growth of an ovarian cancer cell in an individual in need thereof.The method may comprise administering to the individual a polynucleotidesequence which may be selected from the group consisting of

-   -   a) a polynucleotide which may comprise a sequence substantially        complementary (also including 100% complementary over a portion,        e.g., a perfect match) to any of SEQ ID NO.:1 to SEQ ID NO. 49        and 169 or 50,    -   b) a polynucleotide which may comprise a sequence substantially        complementary (also including 100% complementary over a portion,        e.g., a perfect match) to a transcribed or transcribable portion        of any one of SEQ. ID. NOs:1 to 49 and 169 or 50,    -   c) a polynucleotide which may comprise a sequence substantially        complementary (also including 100% complementary over a portion,        e.g., a perfect match) to a translated or translatable portion        of any one of SEQ. ID. NOs:1 to 49 and 169 or 50, and;    -   d) a fragment of any one of a) to c).

The present invention therefore provides in yet another aspect thereof,a siRNA or shRNA molecule that is able to lower the expression of anucleic acid selected from the group consisting of

-   -   a) a polynucleotide which may comprise any one of SEQ ID NO.:1        to SEQ ID NO.:49 and SEQ ID NO.:169, or SEQ ID NO.:50,    -   b) a polynucleotide which may comprise a transcribed or        transcribable portion of any one of SEQ. ID. NOs:1 to 49 and        169, or SEQ ID NO.:50,    -   c) a polynucleotide which may comprise a translated or        translatable portion of any one of SEQ. ID. NOs:1 to 49 and 169        or SEQ ID NO.:50, and;    -   d) a polynucleotide which may comprise a sequence substantially        identical to a), b), or c).

Exemplary embodiment of polynucleotides are those which, for example,may be able to inhibit the growth of an ovarian cancer cell, such as,for example, a polynucleotide having or comprising a sequence selectedfrom the group consisting of any one of SEQ ID NO. 103 to 150. Thesespecific sequences are provided as guidance only and are not intended tolimit the scope of the invention.

The present invention also provides a kit for the diagnosis of cancer.The kit may comprise at least one polynucleotide as described hereinand/or a reagent capable of specifically binding at least onepolynucleotide described herein.

In a further aspect, the present invention relates to an isolatedpolypeptide encoded by the polynucleotide described herein.

The present invention more particularly provides an isolated polypeptidewhich may be selected from the group consisting of

-   -   a) a polypeptide which may comprise any one of SEQ ID NO.:51 to        88 and 170    -   b) a polypeptide which may be encoded by any one of the        polynucleotide described herein,    -   c) a fragment of any one of a) or b),    -   d) a derivative of any one of a) or b) and;    -   e) an analog of any one of a) or b).

In accordance with the present invention, the analog may comprise, forexample, at least one amino acid substitution, deletion or insertion inits amino acid sequence.

The substitution may be conservative or non-conservative. Thepolypeptide analog may be a biologically active analog or an immunogenicanalog which may comprise, for example, at least one amino acidsubstitution (conservative or non conservative), for example, 1 to 5, 1to 10, 1 to 15, 1 to 20, 1 to 50 etc. (including any number therebetween) compared to the original sequence. An immunogenic analog maycomprise, for example, at least one amino acid substitution compared tothe original sequence and may still be bound by an antibody specific forthe original sequence.

In accordance with the present invention, a polypeptide fragment maycomprise, for example, at least 6 consecutive amino acids, at least 8consecutive amino acids or more of an amino acid sequence selected fromthe group consisting of polypeptides encoded by a polynucleotideselected from the group consisting of SEQ ID NO.: 1 to 49 and 169 or anyone of SEQ. ID. NOs:51 to 88 and 170, including variants and analogsthereof. The fragment may be immunogenic and may be used for thepurpose, for example, of generating antibodies.

Exemplary embodiments of polypeptide encompassed by the presentinvention are those which may be encoded by any one of SEQ ID NO.:1-49and 169, more particularly those encoded by any one of SEQ ID NO.:1, 14,16, 19, 20, 22, 28, 37, 41, 45, 46, 47 or 49 and even more particularlythose encoded by any one of SEQ ID NO.: 14, 19, 22, 37, 41, 45, 46 or49.

In a further aspect the present invention relates to a polypeptide whichmay be encoded by the isolated differentially expressed sequence of thepresent invention. The present invention as well relates to thepolypeptide encoded by the non-human ortholog polynucleotide, analogs,derivatives and fragments thereof.

A person skilled in the art may easily determine the possible peptidesequence encoded by a particular nucleic acid sequence as generally, amaximum of 6 possible open-reading frames exist in a particular codingsequence. The first possible open-reading frame may start at the firstnucleotide (5′-3′) of the sequence, therefore using in a 5′ to 3′direction nucleotides No. 1 to 3 as the first codon, using nucleotides 4to 6 as the second codon, etc. The second possible open-reading framemay start at the second nucleotide (5′-3′) of the sequence, thereforeusing in a 5′ to 3′ direction nucleotides No. 2 to 4 as the first codon,using nucleotides 5 to 7 as the second codon, etc. Finally, the thirdpossible open-reading frame may start at the third nucleotide (5′-3′) ofthe sequence, therefore using in a 5′ to 3′ direction nucleotides No. 3to 5 as the first codon, using nucleotides 6 to 8 as the second codon,etc. The fourth possible open-reading frame may start at the firstnucleotide of the sequence in a 3′ to 5′ direction, therefore using in3′ to 5′ direction, nucleotides No. 1 to 3 as the first codon, usingnucleotides 4 to 6 as the second codon, etc. The fifth possibleopen-reading frame may start at the second nucleotide of the sequence ina 3′ to 5′ direction, therefore using in a 3′ to 5′ direction,nucleotides No. 2 to 4 as the first codon, using nucleotides 5 to 7 asthe second codon, etc. Finally, the sixth possible open-reading framemay start at the third nucleotide of the sequence in a 3′ to 5′direction, therefore using in a 3′ to 5′ direction nucleotides No. 3 to5 as the first codon, using nucleotides 6 to 8 as the second codon, etc.

In an additional aspect, the present invention relates to the use of atleast one polypeptide in the manufacture of a composition for theidentification or detection of a cancer cell (tumor cell). Thepolypeptide may be used, for example, as a standard in an assay and/orfor detecting antibodies specific for the particular polypeptide, etc.In yet an additional aspect, the present invention relates to the use ofat least one polypeptide described herein in the identification ordetection of a cancer cell, such as for example, an ovarian cancer cellor any other cancer cell as described herein.

The present invention therefore relates in a further aspect, to the useof at least one polypeptide described herein in the prognosis ordiagnosis of cancer, such as, for example, a malignant ovarian cancer ora low malignant potential ovarian cancer.

As such and in accordance with the present invention, detection of thepolypeptide in a cell (e.g., ovarian cell), tissue (e.g., ovariantissue), sample or body fluid from an individual may preferentially beindicative of a malignant ovarian cancer diagnosis over a low malignantpotential ovarian cancer diagnosis and therefore may preferentially beindicative of a malignant ovarian cancer rather than a low malignantpotential ovarian cancer.

Further in accordance with the present invention, the presence of thepolypeptide in a cell, tissue, sample or body fluid from an individualmay preferentially be indicative of a late-stage malignant ovariancancer.

There is also provided by the present invention, methods for identifyinga cancer cell, which may comprise, for example, contacting a test cell,a test cell sample (cell lysate), a test body fluid (blood, urine,plasma, saliva etc.) or a test tissue with a reagent which may becapable of specifically binding the polypeptide described herein, anddetecting the complex formed by the polypeptide and reagent. Thepresence of a complex may be indicative (a positive indication of thepresence) of a cancer cell such as for example, an ovarian cancer cell,a breast cancer cell, a prostate cancer cell, leukemia, melanoma, arenal cancer cell, a colon cancer cell, a lung cancer cell, a cancercell of the central nervous system and any combination thereof.

The presence of a complex formed by the polypeptide and the specificreagent may be indicative, for example, of ovarian cancer including, forexample, a low malignant potential ovarian cancer or a malignant ovariancancer.

However, the method is more particularly powerful for the detection ofovarian cancer of the malignant type. Therefore, the presence of acomplex may preferentially be indicative of a malignant ovarian cancerrelative (rather than) to a low malignant potential ovarian cancer.

Detection of the complex may also be indicative of a late stagemalignant ovarian cancer.

In accordance with the present invention, the method may also comprise astep of qualitatively or quantitatively comparing the level (amount,presence) of at least one complex present in a test cell, a test sample,a test fluid or a test tissue with the level of complex in a normalcell, a normal cell sample, a normal body fluid, a normal tissue or areference value (e.g., for a non-cancerous condition).

Of course, the presence of more than one polypeptide or complex (twocomplexes or more (multiple complexes)) may be determined, e.g., oneformed by a first specific reagent and a first polypeptide and anotherformed by a second specific reagent and a second polypeptide may bedetected. Detection of more than one polypeptide or complex may help inthe determination of the tumorigenicity of the cell.

An exemplary embodiment of a reagent, which may be used for thedetection of the polypeptide described herein, is an antibody andantibody fragment thereof.

The present invention also relates to a kit which may comprise at leastone of the polypeptide described herein and/or a reagent capable ofspecifically binding to at least one of the polypeptide describedherein.

As one skill in the art will understand, compositions which comprises apolypeptide may be used, for example, for generating antibodies againstthe particular polypeptide, may be used as a reference for assays andkits, etc.

Additional aspects of the invention relates to isolated or purifiedantibodies (including an antigen-binding fragment thereof) which may becapable of specifically binding to a polypeptide selected from the groupconsisting of;

-   -   a) a polypeptide comprising or consisting of any one of SEQ ID        NO.:51 to 89 or 170, and;    -   b) a polypeptide comprising a polypeptide sequence encoded by        any one of the polynucleotide sequence described herein (e.g., a        fragment of at least 6 amino acids of the polypeptide).

More particularly, exemplary embodiments of the present inventionrelates to antibodies which may be capable of specifically binding apolypeptide comprising a polypeptide sequence encoded by any one of SEQID NO.: 1, 14, 16, 19, 20, 22, 28, 37, 41, 45, 46, 47 or 49, or afragment of at least 6 amino acids of the polypeptide.

Even more particular exemplary embodiments of the present inventionrelates to antibodies which may be capable of specifically binding apolypeptide comprising a polypeptide sequence encoded by any one of SEQID NO.: 14, 19, 22, 37, 41, 45, 46 or 49, or a fragment of at least 6amino acids of the polypeptide.

In yet an additional aspect, the present invention relates to ahybridoma cell which is capable of producing an antibody which mayspecifically bind to a polypeptide selected from the group consistingof;

-   -   a) a polypeptide which may comprise any one of SEQ ID NO.:51 to        88, 89 and 170, and;    -   b) a polypeptide which may comprise a polypeptide sequence        encoded by any one of the polynucleotide sequence described        herein or a fragment of at least 6 amino acids of the        polypeptide.

Exemplary hybridoma which are more particularly encompassed by thepresent invention are those which may produce an antibody which may becapable of specifically binding a polypeptide comprising a polypeptidesequence encoded by any one of SEQ ID NO.: 1, 14, 16, 19, 20, 22, 28,37, 41, 45, 46, 47 or 49 or a fragment of at least 6 amino acids of thepolypeptide.

Exemplary embodiments of hybridoma which are even more particularlyencompassed by the present invention are those which may produce anantibody which is capable of specifically binding a polypeptidecomprising a polypeptide sequence encoded by any one of SEQ ID NO.: 14,19, 22, 37, 41, 45, 46 or 49 or a fragment of at least 6 amino acids ofthe polypeptide.

The present invention also relates to a composition which may comprisean antibody described herein.

In a further aspect the present invention provides a method of making anantibody which may comprise immunizing a non-human animal with animmunogenic fragment (at least 6 amino acids, at least 8 amino acids,etc.) of a polypeptide which may be selected, for example, from thegroup consisting of;

-   -   a) a polypeptide which may comprise or consist in any one of SEQ        ID NO.:51 to 88, 89 and 170 or a fragment thereof, and;    -   b) a polypeptide which may comprise a polypeptide sequence        encoded by any one of the polynucleotide sequence described        herein or a portion thereof.

Exemplary polypeptides which may, more particularly, be used forgenerating antibodies are those which are encoded by any one of SEQ IDNO.: 1, 14, 16, 19, 20, 22, 28, 37, 41, 45, 46, 47 or 49 (andpolypeptide comprising a polypeptide fragment of these particular PSEQ).Even more particular polypeptides encompassed by the present inventionare those which are encoded by any one of SEQ ID NO.: 14, 19, 22, 37,41, 45, 46 or 49.

In a further aspect, the present invention relates to a method ofidentifying a compound which is capable of inhibiting the activity orfunction of a polypeptide which may be selected, for example from thegroup consisting of any one of SEQ ID NO.:51 to 88 and 170 or apolypeptide comprising a polypeptide sequence encoded by any one of SEQID NO.:1 to 49 and 169 (e.g., a transcribed portion, a translatedportion, a fragment, substantially identical and even substantiallycomplementary sequences). The method may comprise contacting thepolypeptide with a putative compound an isolating or identifying acompound which is capable of specifically binding any one of the abovementioned polypeptide. The compound may originate from a combinatoriallibrary.

The method may also further comprise determining whether the activity orfunction of the polypeptide (e.g., such as a function indicated at Table2) is affected by the binding of the compound. Those compounds whichcapable of binding to the polypeptide and which and/or which are capableof altering the function or activity of the polypeptide represents adesirable compound to be used in cancer therapy.

The method may also further comprise a step of determining the effect ofthe putative compound on the growth of a cancer cell such as an ovariancancer cell.

The present invention also relates to an assay and method foridentifying a nucleic acid sequence and/or protein involved in thegrowth or development of ovarian cancer. The assay and method maycomprise silencing an endogenous gene of a cancer cell such as anovarian cancer cell and providing the cell with a candidate nucleic acid(or protein). A candidate gene (or protein) positively involved ininducing cancer cell death (e.g., apoptosis) (e.g., ovarian cancer cell)may be identified by its ability to complement the silenced endogenousgene. For example, a candidate nucleic acid involved in ovarian cancerprovided to a cell for which an endogenous gene has been silenced, mayenable the cell to undergo apoptosis more so in the presence of aninducer of apoptosis.

Alternatively, an assay or method may comprise silencing an endogenousgene (gene expression) corresponding to the candidate nucleic acid orprotein sequence to be evaluated and determining the effect of thecandidate nucleic acid or protein on cancer growth (e.g., ovarian cancercell growth). A sequence involved in the promotion or inhibition ofcancer growth, development or malignancy may change the viability of thecell, may change the ability of the cell to grow or to form colonies,etc. The activity of a polypeptide may be impaired by targeting suchpolypeptide with an antibody molecule or any other type of compound.Again, such compound may be identified by screening combinatoriallibraries, phage libraries, etc.

The present invention also provides a method for identifying aninhibitory compound (inhibitor, antagonist) able to impair the function(activity) or expression of a polypeptide described herein. The methodmay comprise, for example, contacting the (substantially purified orisolated) polypeptide or a cell expressing the polypeptide with acandidate compound and measuring the function (activity) or expressionof the polypeptide. A reduction in the function or activity of thepolypeptide (compared to the absence of the candidate compound) may thuspositively identify a suitable inhibitory compound.

In accordance with the present invention, the impaired function oractivity may be associated, for example, with a reduced ability of thepolypeptide to reduce growth of an ovarian cancer cell or a reducedenzymatic activity or function identified for example in Table 2.

The cell used to carry the screening test may not naturally(endogenously) express the polypeptide or analogs, or alternatively theexpression of a naturally expressed polypeptide analog may be repressed.

As used herein the term “sequence identity” relates to (consecutive)nucleotides of a nucleotide sequence with reference to an originalnucleotide sequence which when compared are the same or have a specifiedpercentage of nucleotides which are the same.

The identity may be compared over a region or over the total sequence ofa nucleic acid sequence. Thus, “identity” may be compared, for example,over a region of 10, 19, 20 nucleotides or more (and any numbertherebetween) and more preferably over a longer region or over theentire region of a polynucleotide sequence described at Table 4 (e.g.,any one of SEQ ID NO.:1 to 49 and 169). It is to be understood hereinthat gaps of non-identical nucleotides may be found between identicalnucleic acids regions (identical nucleotides). For example, apolynucleotide may have 100% identity with another polynucleotide over aportion thereof. However, when the entire sequence of bothpolynucleotides is compared, the two polynucleotides may have 50% oftheir overall (total) sequence identity to one another.

Percent identity may be determined, for example, with n algorithm GAP,BESTFIT, or FASTA in the Wisconsin Genetics Software Package Release7.0, using default gap weights.

Polynucleotides of the present invention or portion thereof having fromabout 50 to about 100% and any range therebetween, or about 60 to about100% or about 70 to about 100% or about 80 to about 100% or about 85% toabout 100%, about 90% to about 100%, about 95% to about 100% sequenceidentity with an original polynucleotide are encompassed herewith. It isknown by those of skill in the art, that a polynucleotide having fromabout 50% to 100% identity may function (e.g., anneal to a substantiallycomplementary sequence) in a manner similar to an originalpolynucleotide and therefore may be used in replacement of an originalpolynucleotide. For example a polynucleotide (a nucleic acid sequence)may comprise or have from about 50% to about 100% identity with anoriginal polynucleotide over a defined region and may still work asefficiently or sufficiently to achieve the present invention. The term“substantially identical” used to define the polynucleotides of thepresent invention refers to polynucleotides which have, for example,from 50% to 100% sequence identity and any range therebetween butpreferably at least 80%, at least 85%, at least 90%, at least 95%sequence identity and also include 100% identity with that of anoriginal sequence (including sequences 100% identical over the entirelength of the polynucleotide sequence).

“Substantially identical” polynucleotide sequences may be identified byproviding a probe of about 10 to about 25, or more or about 10 to about20 nucleotides long (or longer) based on the sequence of any one of SEQID NOs.:1 to 49 and 169 (more particularly, a transcribed and/ortranslated portion of any one of SEQ ID NOs.: 1 to 49 and 169) andcomplementary sequence thereof and hybridizing a library ofpolynucleotide (e.g., cDNA or else) originating from another species,tissue, cell, individual etc. A polynucleotide which hybridizes underhighly stringent conditions (e.g., 6×SCC, 65° C.) to the probe may beisolated and identified using methods known in the art. A sequence“substantially identical” includes for example, an isolated allelicvariant, an isolated splice variant, an isolated non-human ortholog, amodified NSEQ etc.

As used herein the terms “sequence complementarity” refers to(consecutive) nucleotides of a nucleotide sequence which arecomplementary to a reference (original) nucleotide sequence. Thecomplementarity may be compared over a region or over the total sequenceof a nucleic acid sequence.

Polynucleotides of the present invention or portion thereof having fromabout 50 to about 100%, or about 60 to about 100% or about 70 to about100% or about 80 to about 100% or about 85%, about 90%, about 95% toabout 100% sequence complementarity with an original polynucleotide arethus encompassed herewith. It is known by those of skill in the art,that a polynucleotide having from about 50% to 100% complementarity withan original sequence may anneal to that sequence in a manner sufficientto carry out the present invention (e.g., inhibit expression of theoriginal polynucleotide).

The term “substantially complementary” used to define thepolynucleotides of the present invention refers to polynucleotides whichhave, for example, from 50% to 100% sequence complementarity and anyrange therebetween but preferably at least 80%, at least 85%, at least90%, at least 95% sequence complementarity and also include 100%complementarity with that of an original sequence (including sequences100% complementarity over the entire length of the polynucleotidesequence).

As used herein the term “polynucleotide” generally refers to anypolyribonucleotide or polydeoxyribo-nucleotide, which may be unmodifiedRNA or DNA, or modified RNA or DNA. “Polynucleotides” include, withoutlimitation single- and double-stranded DNA, DNA that is a mixture ofsingle- and double-stranded regions, single- and double-stranded RNA,and RNA that is a mixture of single- and double-stranded regions, hybridmolecules comprising DNA and RNA that may be single-stranded or, moretypically, double-stranded or a mixture of single- and double-strandedregions. In addition, “polynucleotide” refers to triple-stranded regionscomprising RNA or DNA or both RNA and DNA. The term polynucleotide alsoincludes DNAs or RNAs containing one or more modified bases and DNAs orRNAs with backbones modified for stability or for other reasons.“Modified” bases include, for example, tritylated bases and unusualbases such as inosine. A variety of modifications may be made to DNA andRNA; thus “polynucleotide” embraces chemically, enzymatically ormetabolically modified forms of polynucleotides as typically found ornot in nature, as well as the chemical forms of DNA and RNAcharacteristic of viruses and cells. “Polynucleotide” includes but isnot limited to linear and end-closed molecules. “Polynucleotide” alsoembraces relatively short polynucleotides, often referred to asoligonucleotides.

“Polypeptides” refers to any peptide or protein comprising two or moreamino acids joined to each other by peptide bonds or modified peptidebonds (i.e., peptide isosteres). “Polypeptide” refers to both shortchains, commonly referred as peptides, oligopeptides or oligomers, andto longer chains generally referred to as proteins. As described above,polypeptides may contain amino acids other than the 20 gene-encodedamino acids.

As used herein the term “polypeptide analog” or “analog” relates tomutants, chimeras, fusions, a polypeptide comprising at least one aminoacid deletion, a polypeptide comprising at least one amino acidinsertion or addition, a polypeptide comprising at least one amino acidsubstitutions, and any other type of modifications made relative to agiven polypeptide.

An “analog” is thus to be understood herein as a molecule having abiological activity and/or chemical structure similar to that of apolypeptide described herein. An “analog” may have sequence similaritywith that of an original sequence or a portion of an original sequenceand may also have a modification of its structure as discussed herein.For example, an “analog” may have at least 80% or 85% or 90% sequencesimilarity with an original sequence or a portion of an originalsequence. An “analog” may also have, for example; at least 70% or even50% sequence similarity with an original sequence or a portion of anoriginal sequence and may function in a suitable manner.

A “derivative” is to be understood herein as a polypeptide originatingfrom an original sequence or from a portion of an original sequence andwhich may comprise one or more modification; for example, one or moremodification in the amino acid sequence (e.g., an amino acid addition,deletion, insertion, substitution etc.), one or more modification in thebackbone or side-chain of one or more amino acid, or an addition of agroup or another molecule to one or more amino acids (side-chains orbackbone). Biologically active derivatives of the carrier describedherein are encompassed by the present invention. Also, an “derivative”may have, for example, at least 50%, 70%, 80%, 90% sequence similarityto an original sequence with a combination of one or more modificationin a backbone or side-chain of an amino acid, or an addition of a groupor another molecule, etc.

As used herein the term “biologically active” refers to an analog whichretains some or all of the biological activity of the originalpolypeptide, i.e., to have some of the activity or function associatedwith the polypeptide described at Table 2, or to be able to promote orinhibit the growth ovarian cancer.

Therefore, any polypeptide having a modification compared to an originalpolypeptide which does not destroy significantly a desired activity,function or immunogenicity is encompassed herein. It is well known inthe art, that a number of modifications may be made to the polypeptidesof the present invention without deleteriously affecting theirbiological activity. These modifications may, on the other hand, keep orincrease the biological activity of the original polypeptide or mayoptimize one or more of the particularity (e.g. stability,bioavailability, etc.) of the polypeptides of the present inventionwhich, in some instance might be desirable. Polypeptides of the presentinvention may comprise for example, those containing amino acidsequences modified either by natural processes, such asposttranslational processing, or by chemical modification techniqueswhich are known in the art. Modifications may occur anywhere in apolypeptide including the polypeptide backbone, the amino acidside-chains and the amino- or carboxy-terminus. It will be appreciatedthat the same type of modification may be present in the same or varyingdegrees at several sites in a given polypeptide. Also, a givenpolypeptide may contain many types of modifications. It is to beunderstood herein that more than one modification to the polypeptidesdescribed herein are encompassed by the present invention to the extentthat the biological activity is similar to the original (parent)polypeptide.

As discussed above, polypeptide modification may comprise, for example,amino acid insertion, deletion and substitution (i.e., replacement),either conservative or non-conservative (e.g., D-amino acids, desaminoacids) in the polypeptide sequence where such changes do notsubstantially alter the overall biological activity of the polypeptide.

Example of substitutions may be those, which are conservative (i.e.,wherein a residue is replaced by another of the same general type orgroup) or when wanted, non-conservative (i.e., wherein a residue isreplaced by an amino acid of another type). In addition, a non-naturallyoccurring amino acid may substitute for a naturally occurring amino acid(i.e., non-naturally occurring conservative amino acid substitution or anon-naturally occurring non-conservative amino acid substitution).

As is understood, naturally occurring amino acids may be sub-classifiedas acidic, basic, neutral and polar, or neutral and non-polar.Furthermore, three of the encoded amino acids are aromatic. It may be ofuse that encoded polypeptides differing from the determined polypeptideof the present invention contain substituted codons for amino acids,which are from the same type or group as that of the amino acid to bereplaced. Thus, in some cases, the basic amino acids Lys, Arg and Hismay be interchangeable; the acidic amino acids Asp and Glu may beinterchangeable; the neutral polar amino acids Ser, Thr, Cys, Gln, andAsn may be interchangeable; the non-polar aliphatic amino acids Gly,Ala, Val, Ile, and Leu are interchangeable but because of size Gly andAla are more closely related and Val, Ile and Leu are more closelyrelated to each other, and the aromatic amino acids Phe, Trp and Tyr maybe interchangeable.

It should be further noted that if the polypeptides are madesynthetically, substitutions by amino acids, which are not naturallyencoded by DNA (non-naturally occurring or unnatural amino acid) mayalso be made.

A non-naturally occurring amino acid is to be understood herein as anamino acid which is not naturally produced or found in a mammal. Anon-naturally occurring amino acid comprises a D-amino acid, an aminoacid having an acetylaminomethyl group attached to a sulfur atom of acysteine, a pegylated amino acid, etc. The inclusion of a non-naturallyoccurring amino acid in a defined polypeptide sequence will thereforegenerate a derivative of the original polypeptide. Non-naturallyoccurring amino acids (residues) include also the omega amino acids ofthe formula NH₂(CH₂)_(n)COOH wherein n is 2-6, neutral nonpolar aminoacids, such as sarcosine, t-butyl alanine, t-butyl glycine, N-methylisoleucine, norleucine, etc. Phenylglycine may substitute for Trp, Tyror Phe; citrulline and methionine sulfoxide are neutral nonpolar,cysteic acid is acidic, and ornithine is basic. Proline may besubstituted with hydroxyproline and retain the conformation conferringproperties.

It is known in the art that analogs may be generated by substitutionalmutagenesis and retain the biological activity of the polypeptides ofthe present invention. These analogs have at least one amino acidresidue in the protein molecule removed and a different residue insertedin its place. For example, one site of interest for substitutionalmutagenesis may include but are not restricted to sites identified asthe active site(s), or immunological site(s). Other sites of interestmay be those, for example, in which particular residues obtained fromvarious species are identical. These positions may be important forbiological activity. Examples of substitutions identified as“conservative substitutions” are shown in Table A. If such substitutionsresult in a change not desired, then other type of substitutions,denominated “exemplary substitutions” in Table A, or as furtherdescribed herein in reference to amino acid classes, are introduced andthe products screened.

In some cases it may be of interest to modify the biological activity ofa polypeptide by amino acid substitution, insertion, or deletion. Forexample, modification of a polypeptide may result in an increase in thepolypeptide's biological activity, may modulate its toxicity, may resultin changes in bioavailability or in stability, or may modulate itsimmunological activity or immunological identity. Substantialmodifications in function or immunological identity are accomplished byselecting substitutions that differ significantly in their effect onmaintaining (a) the structure of the polypeptide backbone in the area ofthe substitution, for example, as a sheet or helical conformation. (b)the charge or hydrophobicity of the molecule at the target site, or (c)the bulk of the side chain. Naturally occurring residues are dividedinto groups based on common side chain properties:

(1) hydrophobic: norleucine, methionine (Met), Alanine (Ala), Valine(Val), Leucine (Leu), Isoleucine (Ile)(2) neutral hydrophilic: Cysteine (Cys), Serine (Ser), Threonine (Thr)(3) acidic: Aspartic acid (Asp), Glutamic acid (Glu)(4) basic: Asparagine (Asn), Glutamine (Gin), Histidine (His), Lysine(Lys), Arginine (Arg)(5) residues that influence chain orientation: Glycine (Gly), Proline(Pro); and aromatic: Tryptophan (Trp), Tyrosine (Tyr), Phenylalanine(Phe)

Non-conservative substitutions will entail exchanging a member of one ofthese classes for another.

TABLE A Examplary amino acid substitution Original Conservative residueExemplary substitution substitution Ala (A) Val, Leu, Ile Val Arg (R)Lys, Gln, Asn Lys Asn (N) Gln, His, Lys, Arg Gln Asp (D) Glu Glu Cys (C)Ser Ser Gln (Q) Asn Asn Glu (E) Asp Asp Gly (G) Pro Pro His (H) Asn,Gln, Lys, Arg Arg Ile (I) Leu, Val, Met, Ala, Phe, Leu norleucine Leu(L) Norleucine, Ile, Val, Met, Ile Ala, Phe Lys (K) Arg, Gln, Asn ArgMet (M) Leu, Phe, Ile Leu Phe (F) Leu, Val, Ile, Ala Leu Pro (P) Gly GlySer (S) Thr Thr Thr (T) Ser Ser Trp (W) Tyr Tyr Tyr (Y) Trp, Phe, Thr,Ser Phe Val (V) Ile, Leu, Met, Phe, Ala, Leu norleucine

It is to be understood herein, that if a “range” or “group” ofsubstances (e.g. amino acids), substituents” or the like is mentioned orif other types of a particular characteristic (e.g. temperature,pressure, chemical structure, time, etc.) is mentioned, the presentinvention relates to and explicitly incorporates herein each and everyspecific member and combination of sub-ranges or sub-groups thereinwhatsoever. Thus, any specified range or group is to be understood as ashorthand way of referring to each and every member of a range or groupindividually as well as each and every possible sub-ranges or sub-groupsencompassed therein; and similarly with respect to any sub-ranges orsub-groups therein. Thus, for example, with respect to a percentage (%)of identity of from about 80 to 100%, it is to be understood asspecifically incorporating herein each and every individual %, as wellas sub-range, such as for example 80%, 81%, 84.78%, 93%, 99% etc. withrespect to a length of “about 10 to about 25” it is to be understood asspecifically incorporating each and every individual number such as forexample 10, 11, 12, 13, 14, 15 up to and including 25; and similarlywith respect to other parameters such as, concentrations, elements, etc.

Other objects, features, advantages, and aspects of the presentinvention will become apparent to those skilled in the art from thefollowing description. It should be understood, however, that thefollowing description and the specific examples, while indicatingpreferred embodiments of the invention, are given by way of illustrationonly. Various changes and modifications within the spirit and scope ofthe disclosed invention will become readily apparent to those skilled inthe art from reading the following description and from reading theother parts of the present disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

In the appended drawings:

FIG. 1 to FIG. 31, FIG. 33, FIG. 34, FIG. 36, FIG. 37, FIG. 39, FIG. 40,FIG. 42, FIG. 43, FIG. 46, FIG. 47, FIG. 49, FIG. 50 and FIG. 56 arepictures of macroarray hybridization results showing the differentialexpression data for STAR selected ovarian cancer-related humansequences. Macroarrays were prepared using RAMP amplified RNA from sixhuman LMP samples (A-F 1) and twenty malignant ovarian tumor samples(Table B) (A-F 2 and A-G 3-4), and 30 different normal human tissues(adrenal (A7), breast (B7), jejunum (C7), trachea (D7), liver (E7),placenta (F7), aorta (G7), brain (H7), lung (A8), adrenal cortex (B8),esophagus (C8), colon (D8), ovary (E8), kidney (F8), prostate (G8),thymus (H8), skeletal muscle (A9), vena cava (B9), stomach (C9), smallintestine (D9), heart (E9), fallopian tube (F9), spleen (G9), bladder(H9), cervix (A10), pancreas (B10), ileum (010), duodenum (D10), thyroid(E10) and testicle (F10)). Also included on the RNA macroarray werebreast cancer cell lines (MDA (A5), MCF7 (B5) and MCF7+estradiol (C5))and LCM microdissected prostate normal epithelium (A-C 6) and prostatecancer (D-F 6), prostate cancer cell line, LNCap (G6) and LNCap+androgen(H6). In these figures, the probe labeling reaction was also spiked witha dsDNA sequence for Arabidopsis, which hybridizes to the same sequencespotted on the macroarray (M) in order to serve as a control for thelabeling reaction.

FIG. 32, FIG. 35, FIG. 38, FIG. 41, FIG. 44, FIG. 45 and FIG. 48 arepictures of RT-PCR results showing the differential expression data forSTAR selected ovarian cancer-related human sequences. Complimentary DNAswere prepared using random hexamers from RAMP amplified RNA from sixhuman LMP samples and at least twenty malignant ovarian tumor samples(Table B) as indicated in the figures. The cDNAs were quantified andused as templates for PCR with gene-specific primers using standardmethods known to those skilled in the art.

FIG. 57 to FIG. 105 are pictures of RT-PCR results showing thedifferential expression data for STAR selected cancer-related humansequences in RNA samples derived from the NCI-60 panel of cancer celllines. These 59 cell lines are derived from tumors that encompass 9human cancer types that include leukemia, the central nervous system,breast, colon, lung, melanoma, ovarian, prostate, and renal.Complimentary DNAs were prepared using random hexamers from RAMPamplified RNA from 59 human cancer cell lines (Table C). The cDNAs werequantified and used as templates for PCR with gene-specific primersusing standard methods known to those skilled in the art. For each PCRresult depicted in FIG. 57 to FIG. 105, equal amounts of template cDNAused in each PCR reaction was confirmed by reamplifying GAPDH with aspecific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO.167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for thishousekeeping gene.

More particularly,

FIG. 1 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 1. The STAR dsDNA clone representing SEQ. ID. NO. 1was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Expression of this sequence was only observed in one (placenta (F7))of the 30 normal tissues and the breast cancer cell line, MCF7 (B-C 5);

FIG. 2 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 2. The STAR dsDNA clone representing SEQ. ID. NO. 2was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Expression of this sequence was also evident in six (breast (B7),placenta (F7), aorta (G7), colon (D8), ovary (E8) and thymus (H8)) ofthe 30 normal tissues;

FIG. 3 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 3. The STAR dsDNA clone representing SEQ. ID. NO. 3was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples(A-F 1) but overall, only low levels of expression. No significantexpression was seen in any of the normal tissues;

FIG. 4 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 4. The STAR dsDNA clone representing SEQ. ID. NO. 4was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Expression of this sequence was also evident in two (esophagus (C8)and fallopian tube (F9)) of the 30 normal tissues;

FIG. 5 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 5. The STAR dsDNA clone representing SEQ. ID. NO. 5was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Weak expression of this sequence similar to that of LMPs was alsoobserved in many of the normal tissues;

FIG. 6 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 6. The STAR dsDNA clone representing SEQ. ID. NO. 6was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Expression of this sequence was also evident in three (liver (E7),placenta (F7) and kidney (F8)) of the 30 normal tissues;

FIG. 7 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 7. The STAR dsDNA clone representing SEQ. ID. NO. 7was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in several malignant ovariancancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1).Expression of this sequence was only evident in one (testicle (F10)) ofthe 30 normal tissues;

FIG. 8 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 8. The STAR dsDNA clone representing SEQ. ID. NO. 8was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Expression of this sequence was only evident in two (esophagus (C8)and stomach (C9)) of the 30 normal tissues and the breast and prostatecancer cell lines, MDA (A5) and LNCap (G6 and H6), respectively;

FIG. 9 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 9. The STAR dsDNA clone representing SEQ. ID. NO. 9was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Expression of this sequence was only evident in one (placenta (F7))of the 30 normal tissues, the breast cancer cell line, MCF7 (B-C 5) andLCM microdissected prostate cancer samples (D6 and F6);

FIG. 10 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 10. The STAR dsDNA clone representing SEQ. ID. NO. 10was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Expression of this sequence was only evident in one (testicle (F10))of the 30 normal tissues, the breast cancer cell lines, MDA (A5) andMCF7 (B-C 5) and prostate cancer cell line, LNCap (G-H 6);

FIG. 11 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 11. The STAR dsDNA clone representing SEQ. ID. NO. 11was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was only evident in thebreast cancer cell lines, MDA (A5) and MCF7 (B-C 5);

FIG. 12 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 12. The STAR dsDNA clone representing SEQ. ID. NO. 12was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in the majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was only evident in one(testicle (F10)) of the 30 normal tissues and the prostate cancer cellline, LNCap (G-H 6). Weaker expression was also observed in normal ovary(E8);

FIG. 13 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 13. The STAR dsDNA clone representing SEQ. ID. NO. 13was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was only evident in thebreast cancer cell lines, MDA (A5) and MCF7 (B-C 5). Weaker expressionwas also observed in some normal tissues and the prostate cancer cellline, LNCap (G-H 6);

FIG. 14 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 14. The STAR dsDNA clone representing SEQ. ID. NO. 14was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Weaker expression of this sequence was only observed in the normalkidney (F8) tissue;

FIG. 15 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 15. The STAR dsDNA clone representing SEQ. ID. NO. 15was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in the majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Weaker expression of this sequence similar to that of the LMPs wasnoted in many of the normal tissues as well;

FIG. 16 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 16. The STAR dsDNA clone representing SEQ. ID. NO. 16was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in the majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell lines, MDA (A5) and MCF7 (B-C 5). Weaker expressionsimilar to that of the LMPs was seen in prostate and some normal tissuesamples;

FIG. 17 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 17. The STAR dsDNA clone representing SEQ. ID. NO. 17was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in the majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was only evident in two(breast (B7) and bladder (H9)) of the 30 normal tissues;

FIG. 18 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 18. The STAR dsDNA clone representing SEQ. ID. NO. 18was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell lines, MDA (A5) and MCF7 (B-C 5), and somewhat lowerexpression in prostate cancer cell line, LNCap (G-H 6) and eight normaltissues (adrenal (A7), placenta (F7), lung (A8), adrenal cortex (B8),esophagus (C8), colon (D8), ovary (E8) and testicle (F10));

FIG. 19A is a picture of the macroarray hybridization results showingthe differential expression data for STAR selected ovariancancer-related human SEQ. ID. NO. 19. The STAR dsDNA clone representingSEQ. ID. NO. 19 was labeled with ³²P and hybridized to the macroarray.The hybridization results obtained confirm its upregulation in severalmalignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMPsamples (A-F 1). Significant expression of this sequence was also onlyevident in the breast cancer cell line, MCF7 (B-C 5);

FIG. 19B (panels A and B) is a picture of RT-PCR data showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 19 and KCNMB2 gene belonging to Unigene cluster,Hs.478368. Primer pairs specific to either the STAR clone sequence forSEQ. ID. NO. 19 or the KCNMB2 gene were used to perform RT-PCR on normalovarian tissue, and benign and different stages/grades of ovariancancer. As indicated by the expected PCR amplicon product (FIG. 19B,panel A), compared to normal (Lane 1), benign (Lanes 2-3) and LMPs(Lanes 4-7) samples, increased expression of SEQ. ID. NO. 19 mRNA wasevident in clear cell carcinoma (Lanes 8-9), late stage endometrioid(Lane 12) and malignant serous (Lanes 15-17). These results confirm theupregulation of the gene expression for SEQ. ID. NO. 19 in malignantovarian cancer. However, the expression of KCNMB2 was markedly differentfrom that of SEQ. ID. NO. 19 showing essentially no difference in itsexpression amongst the different ovarian samples (FIG. 19B, panel B);

FIG. 20 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 20. The STAR dsDNA clone representing SEQ. ID. NO. 20was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in several malignant ovariancancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1).Significant expression of this sequence was also evident in the four(jejunum (C7), trachea (D7), colon (D8) and thymus (H8)) of the 30normal tissues;

FIG. 21 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 21. The STAR dsDNA clone representing SEQ. ID. NO. 21was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thethree (adrenal (A7), breast (B7) and aorta (G7)) of the 30 normaltissues;

FIG. 22 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 22. The STAR dsDNA clone representing SEQ. ID. NO. 22was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell line, MCF7 (B-C 5). Weaker expression similar to thatof the LMPs was seen in a majority of the normal tissues;

FIG. 23 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 23. The STAR dsDNA clone representing SEQ. ID. NO. 23was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in several malignant ovariancancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1).Significant expression of this sequence was also evident in the breastcancer cell lines, MDA (A5) and MCF7 (B-C 5) and prostate cancer cellline, LNCap (G-H 6);

FIG. 24 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 24. The STAR dsDNA clone representing SEQ. ID. NO. 24was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in several of the malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell line, MCF7 (B-C 5);

FIG. 25 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 25. The STAR dsDNA clone representing SEQ. ID. NO. 25was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in theprostate cancer cell line, LNCap (G-H 6);

FIG. 26 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 26. The STAR dsDNA clone representing SEQ. ID. NO. 26was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell lines, MDA (A5) and MCF7 (B-C 5), prostate cancercell line, LNCap (G-H 6) and one normal tissue, testicle (F10). Weakerexpression similar to that of the LMPs was seen in some normal tissuesas well;

FIG. 27 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 27. The STAR dsDNA clone representing SEQ. ID. NO. 27was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell lines, MDA (A5) and MCF7 (B-C 5), prostate cancercell line, LNCap (G-H 6). Weaker expression similar to that of the LMPswas seen in seven (adrenal (A7), placenta (F7), lung (A8), esophagus(C8), colon (D8), ovary (E8) and testicle (F10)) of the 30 normaltissues as well;

FIG. 28 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 28. The STAR dsDNA clone representing SEQ. ID. NO. 28was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell lines, MDA (A5) and MCF7 (B-C 5). Weaker expressionsimilar to that of LMPs was seen for all other tissues;

FIG. 29 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 29. The STAR dsDNA clone representing SEQ. ID. NO. 29was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell line, MCF7 (B-C 5) and three (breast (B7), esophagus(C8) and fallopian tube (F9)) of the 30 normal tissues;

FIG. 30 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 30. The STAR dsDNA clone representing SEQ. ID. NO. 30was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell line, MCF7 (B-C 5), prostate cancer samples (D-H 6).Weaker expression similar to that of LMPs was seen in only very fewnormal tissues;

FIG. 31 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 31. The STAR dsDNA clone representing SEQ. ID. NO. 31was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in thebreast cancer cell line, MCF7 (B-C 5), prostate cancer samples (D-H 6).Weaker expression similar to that of LMPs was seen in only very fewnormal tissues;

FIG. 32 is a picture of RT-PCR data showing the differential expressiondata for STAR selected ovarian cancer-related human SEQ. ID. NO. 32. Forthis gene, the macroarray data was not available. A primer pair, OGS1077 (GCGTCCGGGCCTGTCTTCAACCT; SEQ. ID. NO. 153) and OGS 1078(GCCCCACCCTCTACCCCACCACTA; SEQ. ID. NO. 154) for SEQ. ID. NO. 32 wasused to perform RT-PCR on normal ovarian tissue, and benign anddifferent stages/grades of ovarian cancer. As indicated by the expectedPCR amplicon product, compared to normal (Lane 1) and benign (Lanes2-3), increased expression of SEQ. ID. NO. 32 mRNA was evident in LMPs(Lanes 4-7), clear cell carcinoma (Lanes 8-9), late stage endometrioid(Lane 12) and malignant serous (Lanes 15-17). These results confirm theupregulation of the gene expression for SEQ. ID. NO. 32 in malignantovarian cancer;

FIG. 33 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 33. The STAR dsDNA clone representing SEQ. ID. NO. 33was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in theprostate cancer samples (B-F 6). Weaker expression was seen in manynormal tissues and strong expression was seen trachea (D7), colon (D8),small intestine (D9), thymus (H8) and spleen (G9). These results confirmthe upregulation of the gene expression for SEQ. ID. NO. 33 in malignantovarian cancer;

FIG. 34 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 34. The STAR dsDNA clone representing SEQ. ID. NO. 34was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in theprostate cancer samples (B-F 6). Weaker expression was seen in manynormal tissues and strong expression was seen trachea (D7), colon (D8),small intestine (D9), thymus (H8) and spleen (G9). These results confirmthe upregulation of the gene expression for SEQ. ID. NO. 34 in malignantovarian cancer;

FIG. 35 is a picture of RT-PCR data showing the differential expressiondata for STAR selected ovarian cancer-related human SEQ. ID. NO. 35. Forthis gene, the macroarray data was not available. A primer pair, OGS1141 (GAGATCCTGATCAAGGTGCAGG; SEQ. ID. NO. 155) and OGS 1142(TGCACGCTCACAGCAGTCAGG; SEQ. ID. NO. 156) for SEQ. ID. NO. 35 was usedto perform RT-PCR on LMP samples, different stages/grades of ovariancancer and normal human tissue samples. As indicated by the expected PCRamplicon product (indicated as AB-0201), increased expression of SEQ.ID. NO. 35 mRNA was evident in some ovarian cancer lanes (lanes 10, 11,14, 18, 28 and 29) and the mRNA was not expressed in LMP samples.Expression was observed in only one normal tissue sample, ileum (lane27). Equal amounts of template cDNA used in each PCR reaction wasconfirmed by reamplifying GAPDH with a specific primer pair, OGS 315(TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316(CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene.These results confirm the upregulation of the gene expression for SEQ.ID. NO. 35 in malignant ovarian cancer;

FIG. 36 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 36. The STAR dsDNA clone representing SEQ. ID. NO. 36was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a few of the malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). No expression was seen in other cancer types nor in normal humantissues. These results confirm the upregulation of the gene expressionfor SEQ. ID. NO. 36 in malignant ovarian cancer;

FIG. 37 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 37. The STAR dsDNA clone representing SEQ. ID. NO. 37was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Weak expression of this sequence was also evident in the prostatecancer samples (B-F 6). Weaker expression was seen in some normaltissues. These results confirm the upregulation of the gene expressionfor SEQ. ID. NO. 37 in malignant ovarian cancer;

FIG. 38 is a picture of RT-PCR data showing the differential expressiondata for STAR selected ovarian cancer-related human SEQ. ID. NO. 38. Forthis gene, the macroarray data was not available. A primer pair, OGS1202 (AACATGACTAAGATGCCCAACC; SEQ. ID. NO. 157) and OGS 1203(AATCTCCTTCACCTCCACTACTG; SEQ. ID. NO. 158) for SEQ. ID. NO. 38 was usedto perform RT-PCR on LMP samples, different stages/grades of ovariancancer and normal human tissue samples. As indicated by the expected PCRamplicon product (indicated as AB-0332), increased expression of SEQ.ID. NO. 38 mRNA was evident in approximately half of the ovarian cancerlanes and weaker expression was seen in LMP samples. Expression wasobserved in many normal tissue samples. Equal amounts of template cDNAused in each PCR reaction was confirmed by reamplifying GAPDH with aspecific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO.167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for thishousekeeping gene. These results confirm the upregulation of the geneexpression for SEQ. ID. NO. 38 in malignant ovarian cancer;

FIG. 39 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 39. The STAR dsDNA clone representing SEQ. ID. NO. 39was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Strong expression was also observed in breast cancer samples (A-C 5)and weak expression in prostate cancer samples (A-H 6). Weakerexpression was seen in a few normal tissues with strong expression intestes (F 10). These results confirm the upregulation of the geneexpression for SEQ. ID. NO. 39 in malignant ovarian cancer;

FIG. 40 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 40. The STAR dsDNA clone representing SEQ. ID. NO. 40was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Weak expression was seen in a few normal tissues with strongexpression in kidney (F 8). These results confirm the upregulation ofthe gene expression for SEQ. ID. NO. 40 in malignant ovarian cancer;

FIG. 41 is a picture of RT-PCR data showing the differential expressiondata for STAR selected ovarian cancer-related human SEQ. ID. NO. 41. Forthis gene, the macroarray data was not available. A primer pair, OGS1212 (AAGCATAGCCATAGGTGATTGG; SEQ. ID. NO. 159) and OGS 1213(ACAGGTATCAGACAAGGGAGCAG; SEQ. ID. NO. 160) for SEQ. ID. NO. 41 was usedto perform RT-PCR on LMP samples, different stages/grades of ovariancancer and normal human tissue samples. As indicated by the expected PCRamplicon product (indicated as AB-0532), increased expression of SEQ.ID. NO. 41 mRNA was evident in a large majority of the ovarian cancerlanes and weaker expression was seen in LMP samples. Expression wasobserved in a few normal tissue samples such as kidney, thymus andspleen (lanes 14, 16 and 23, respectively). Equal amounts of templatecDNA used in each PCR reaction was confirmed by reamplifying GAPDH witha specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID.NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) forthis housekeeping gene. These results confirm the upregulation of thegene expression for SEQ. ID. NO. 41 in malignant ovarian cancer;

FIG. 42 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 42. The STAR dsDNA clone representing SEQ. ID. NO. 42was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained showed its expression in both malignant ovarian cancersamples (A-F 2 and A-G 3-4) and LMP samples (A-F 1). Weak expression wasalso observed in breast cancer samples (A-C 5). Weak expression was seenin a few normal tissues with moderate expression in placenta (F 7).These results confirm the expression for SEQ. ID. NO. 42 in malignantovarian cancer;

FIG. 43 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 43. The STAR dsDNA clone representing SEQ. ID. NO. 43was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Strong expression was also observed in breast cancer samples (A-C 5)and weak expression in prostate cancer samples (A-H 6). Weakerexpression was seen in normal tissues with strong expression in testes(F 10). These results confirm the upregulation of the gene expressionfor SEQ. ID. NO. 43 in malignant ovarian cancer;

FIG. 44 is a picture of RT-PCR data showing the differential expressiondata for STAR selected ovarian cancer-related human SEQ. ID. NO. 44. Forthis gene, the macroarray data was not available. A primer pair, OGS1171 (TTACGACCTATTTCTCCGTGG; SEQ. ID. NO. 161) and OGS 1172(AATGCAATAATTGGCCACTGC; SEQ. ID. NO. 162) for SEQ. ID. NO. 44 was usedto perform RT-PCR on LMP samples, different stages/grades of ovariancancer and normal human tissue samples. As indicated by the expected PCRamplicon product (indicated as AB-0795), increased expression of SEQ.ID. NO. 44 mRNA was evident in a large majority of the ovarian cancerlanes and weaker expression was seen in LMP samples. Expression wasobserved in several normal tissue samples such as aorta, skeletalmuscle, small intestine and spleen (lanes 7, 17, 20 and 23,respectively). Equal amounts of template cDNA used in each PCR reactionwas confirmed by reamplifying GAPDH with a specific primer pair, OGS 315(TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316(CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene.These results confirm the upregulation of the gene expression for SEQ.ID. NO. 44 in malignant ovarian cancer;

FIG. 45 is a picture of RT-PCR data showing the differential expressiondata for STAR selected ovarian cancer-related human SEQ. ID. NO. 45. Forthis gene, the macroarray data was not available. A primer pair, OGS1175 (ACACATCAAACTGCTTATCCAGG; SEQ. ID. NO. 163) and OGS 1176(ACTGATGTGAAAATGCACATCC; SEQ. ID. NO. 164) for SEQ. ID. NO. 45 was usedto perform RT-PCR on LMP samples, different stages/grades of ovariancancer and normal human tissue samples. As indicated by the expected PCRamplicon product (indicated as AB-0846), increased expression of SEQ.ID. NO. 45 mRNA was evident in half of the ovarian cancer lanes andweaker expression was seen in LMP samples. Expression was observed inonly a few normal tissue samples such as kidney, fallopian tube andtestes (lanes 14, 22 and 30, respectively). Equal amounts of templatecDNA used in each PCR reaction was confirmed by reamplifying GAPDH witha specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID.NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) forthis housekeeping gene. These results confirm the upregulation of thegene expression for SEQ. ID. NO. 45 in malignant ovarian cancer;

FIG. 46 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 46. The STAR dsDNA clone representing SEQ. ID. NO. 46was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Weak expression was also observed in prostate cancer samples (A-H6). Weaker expression was seen in a few normal tissues with moderateexpression in breast (B 7) and ovary (E 8). These results confirm theupregulation of the gene expression for SEQ. ID. NO. 46 in malignantovarian cancer;

FIG. 47 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 47. The STAR dsDNA clone representing SEQ. ID. NO. 47was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in theprostate cancer samples (B-F 6). Weaker expression was seen in manynormal tissues and strong expression was seen trachea (D7), colon (D8),small intestine (D9), thymus (H8) and spleen (G9). These results confirmthe upregulation of the gene expression for SEQ. ID. NO. 47 in malignantovarian cancer;

FIG. 48 is a picture of RT-PCR data showing the differential expressiondata for STAR selected ovarian cancer-related human SEQ. ID. NO. 48. Forthis gene, the macroarray data was not available. A primer pair, OGS1282 (ATGGCTCATACAGCACTCAGG; SEQ. ID. NO. 165) and OGS 1283(GAACTGTCACTCCGGAAAGCCT; SEQ. ID. NO. 166) for SEQ. ID. NO. 48 was usedto perform RT-PCR on LMP samples, different stages/grades of ovariancancer and normal human tissue samples. As indicated by the expected PCRamplicon product (indicated as AB-1120), increased expression of SEQ.ID. NO. 48 mRNA was evident in a majority of the ovarian cancer lanesand weaker expression was seen in LMP samples. Expression was evident invirtually all normal tissues. Equal amounts of template cDNA used ineach PCR reaction was confirmed by reamplifying GAPDH with a specificprimer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) andOGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for thishousekeeping gene. These results confirm the upregulation of the geneexpression for SEQ. ID. NO. 48 in malignant ovarian cancer;

FIG. 49 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 49. The STAR dsDNA clone representing SEQ. ID. NO. 49was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Strong expression was also observed in breast cancer samples (A-C 5)and weak expression in prostate cancer samples (A-H 6). Weakerexpression was seen in normal tissues. These results confirm theupregulation of the gene expression for SEQ. ID. NO. 49 in malignantovarian cancer;

FIG. 50 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 50. The STAR dsDNA clone representing SEQ. ID. NO. 50was labeled with ³²P and hybridized to the macroarray. The hybridizationresults obtained confirm its upregulation in a majority of malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Significant expression of this sequence was also evident in theseven (adrenal (A7), breast (B7), trachea (D7), placenta (F7), lung(A8), kidney (F8) and fallopian tube (F9)) of the 30 normal tissues;

FIG. 51 is a picture showing an example of STAR subtraction for theovarian cancer samples. The housekeeping genes, GAPDH (Panel A) andβ-actin (Panel B) were nicely subtracted for both LMP minus Malignant(SL133 to SL137) and Malignant minus LMP (SL123 to SL127) whereas, aknown differentially expressed upregulated gene, CCNE1 (Panel C) inmalignant ovarian tumors was not subtracted in Malignant minus LMP STARlibraries but instead, enriched (Lanes SL123 to SL127 compared to Lanes6 to 10);

FIG. 52 is a picture showing the effect of shRNAs on the expression ofendogenous genes encoded by SEQ.ID Nos. 1 and 3 in transfected TOV-21Gcells. Two shRNAs per SEQ.ID. were transfected in TOV-21G ovarian cancercell lines and monitored by RT-PCR using gene-specific primers. In eachcase, both shRNAs attenuated the expression of the genes;

FIG. 53 is a picture showing the effect of SEQ.ID.-specific shRNAs onthe proliferation of TOV-21G cells. Decreased proliferation isindicative of a gene that, when attenuated, is required for normalgrowth of the cancer cells. The cells were stably transfected with twoseparate shRNA expression vectors and the proliferation of the cells wasmeasured in an MTT assay. The positive control plasmid expresses a shRNAthat has homology to no known gene in humans;

FIG. 54 is a picture showing SEQ.ID.-specific shRNAs on the survival ofTOV-21G cells. Less staining is indicative of a gene that, whenattenuated, is required for survival of the cancer cells in this assay.The cells were transiently transfected with two separate shRNAexpression vectors and the remaining colonies were stained with crystalviolet and photographed. The positive control plasmid expresses a shRNAthat has homology to no known gene in humans;

FIGS. 55A and 55B are pictures of RT-PCR data showing the differentialexpression data for STAR selected ovarian cancer-related human SEQ. ID.NO. 01, 09, 12, 15, 17, 19, 20 and 24. To further demonstrate that theSTAR SEQ. ID. NOs. selected after macroarray analysis were upregulatedin malignant ovarian cancer samples compared to LMPs and normal ovariansamples, semi-quantitative RT-PCR was performed for 25 cycles usingHotStarTaq polymerase according to the supplier instructions (Qiagen).Furthermore, these results serve to demonstrate the utility of thesesequences as potential diagnostic, prognostic or theranostic markers forovarian cancer. For SEQ. ID. NOs. 01, 09, 12, 15, 17, 19, 20 and 24, aspecific primer pair for each was used. The differential expressionresults obtained for each SEQ. ID. NO. tested are shown in FIGS. 55A and55B. As indicated by the expected PCR amplicon product for each SEQ. ID.NO., there is a clear tendency towards increased expression of the mRNAscorresponding to SEQ. ID. NOs. 01, 09, 12, 15, 17, 19, 20 and 24 inclear cell carcinoma (Lanes 8-9), late stage endometrioid (Lane 12) anddifferent stages of malignant serous (Lanes 15-17) compared to normal(Lane 1), benign (Lanes 2-3) and LMPs (Lanes 4-7) ovarian samples. Theseresults confirm the upregulation of the gene expression for SEQ. ID.NOs. 01, 09, 12, 15, 17, 19, 20 and 24 in the different stages ofmalignant ovarian cancer as was observed using the macroarrays;

FIG. 56 is a picture of the macroarray hybridization results showing thedifferential expression data for STAR selected ovarian cancer-relatedhuman SEQ. ID. NO. 169. The STAR dsDNA clone representing SEQ. ID. NO.169 was labeled with ³²P and hybridized to the macroarray. Thehybridization results obtained confirm its upregulation in malignantovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F1). Weaker expression was seen in some normal tissues and strongexpression was seen liver (E7) and aorta (G7). These results confirm theupregulation of the gene expression for SEQ. ID. NO. 169 in malignantovarian cancer;

FIG. 57 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 1in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1136 (GCTTAAAAGAGTCCTCCTGTGGC; SEQ. ID. NO. 171) andOGS 1044 (TGGACATTGTTCTTAAAGTGTGG; SEQ. ID. NO. 172) for SEQ. ID. NO. 1was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 1 mRNA was evident in ovarian,renal, lung, colon, breast cancers and weaker expression was seen inmelanoma samples;

FIG. 58 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 2in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1250 (AGGTTTTATGGCCACCGTCAG; SEQ. ID. NO. 173) and OGS1251 (ATCCTATACCGCTCGGTTATGC; SEQ. ID. NO. 174) for SEQ. ID. NO. 2 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 2 mRNA was evident in all ninecancer types but weaker expression was seen in melanoma and leukemiasamples;

FIG. 59 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 3in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1049 (GGGCGGCGGCTCTTTCCTCCTC; SEQ. ID. NO. 175) and OGS1050 (GCTAGCGGCCCCATACTCG; SEQ. ID. NO. 176) for SEQ. ID. NO. 3 was usedto perform RT-PCR. As indicated by the expected PCR amplicon, increasedexpression of SEQ. ID. NO. 3 mRNA was evident in eight cancer types andabsent in the leukemia samples;

FIG. 60 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 4in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1051 (ACACTGGATGCCCTGAATGACACA; SEQ. ID. NO. 177) andOGS 1052 (GCTTTGGCCCTTTTTGCTAA; SEQ. ID. NO. 178) for SEQ. ID. NO. 4 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 4 mRNA was evident in melanoma,ovarian, CNS, and lung cancers and weakly expressed in the leukemiasamples;

FIG. 61 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 5in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1252 (CCCACTTCTGTCTTACTGCATC; SEQ. ID. NO. 179) and OGS1253 (CATAGTACTCCAGGGCTTATTC; SEQ. ID. NO. 180) for SEQ. ID. NO. 4 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 5 mRNA was evident all cancertypes;

FIG. 62 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 6in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1083 (AACGATTGCCCGGATTGATGACA; SEQ. ID. NO. 181) andOGS 1084 (TACTTGAGGCTGGGGTGGGAGATG; SEQ. ID. NO. 182) for SEQ. ID. NO. 6was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 6 mRNA was evident all cancertypes;

FIG. 63 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 7in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1053 (CACTACGCCAGGCACCCCCAAAAC; SEQ. ID. NO. 183) andOGS 1054 (CGAGGCGCACGGCAGTCT; SEQ. ID. NO. 184) for SEQ. ID. NO. 7 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 7 mRNA was evident only in ovariancancer samples;

FIG. 64 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 8in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1037 (ATCCGTTGCTGCAGCTCGTTCCTC; SEQ. ID. NO. 185) andOGS 1038 (ACCCTGCTGACCTTCTTCCATTCC; SEQ. ID. NO. 186) for SEQ. ID. NO. 8was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 8 mRNA was evident in all cancertypes;

FIG. 65 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 9in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1045 (TCGGAGGAGGGCTGGCTGGTGTTT; SEQ. ID. NO. 187) andOGS 1046 (CTTGGGCGTCTTGGAGCGGTTCTG; SEQ. ID. NO. 188) for SEQ. ID. NO. 9was used to perform RT-PCR. As indicated by the expected PCR amplicon,(lower band on the gel; the top band is an artifact of the PCR reaction)increased expression of SEQ. ID. NO. 9 mRNA was evident in ovarian,lung, colon, breast cancer, and melanoma and weakly expressed inleukemia and CNS cancer;

FIG. 66 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 10in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1240 (AGAGCCTATTGAAGATGAACAG; SEQ. ID. NO. 189) and OGS1241 (TGATTGCCCCGGATCCTCTTAGG; SEQ. ID. NO. 190) for SEQ. ID. NO. 10 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 10 mRNA was evident in all cancertypes;

FIG. 67 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 11in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1304 (GGACAAATACGACGACGAGG; SEQ. ID. NO. 191) and OGS1305 (GGTTTCTTGGGTAGTGGGC; SEQ. ID. NO. 192) for SEQ. ID. NO. 11 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 11 mRNA was evident in all cancertypes;

FIG. 68 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 12in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1039 (CCCCGGAGAAGGAAGAGCAGTA; SEQ. ID. NO. 193) and OGS1040 (CGAAAGCCGGCAGTTAGTTATTGA; SEQ. ID. NO. 194) for SEQ. ID. NO. 12was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 12 mRNA was evident in all cancertypes but weakly in CNS cancer and leukemia;

FIG. 69 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 13in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1095 (GGCGGGCAACGAATTCCAGGTGTC; SEQ. ID. NO. 195) andOGS 1096 (TCAGAGGTTCGTCGCATTTGTCCA; SEQ. ID. NO. 196) for SEQ. ID. NO.13 was used to perform RT-PCR. As indicated by the expected PCRamplicon, increased expression of SEQ. ID. NO. 13 mRNA was evident inall cancer types;

FIG. 70 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 15in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1284 (CAACAGTCATGATGTGTGGATG; SEQ. ID. NO. 197) and OGS1285 (ACTGCACCTTGTCCGTGTTGAC; SEQ. ID. NO. 198) for SEQ. ID. NO. 15 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 15 mRNA was evident in ovarian,prostate, lung, colon, and breast cancer;

FIG. 71 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 16in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1063 (CCGGCTGGCTGCTTTGTTTA; SEQ. ID. NO. 199) and OGS1064 (ATGATCAGCAGGTTCGTTGGTAGG; SEQ. ID. NO. 200) for SEQ. ID. NO. 16was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 16 mRNA was evident in ovarian,lung, colon, and breast cancer;

FIG. 72 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 17in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1031 (ATGCCGGAAGTGAATGTGG; SEQ. ID. NO. 201) and OGS1032 (GGTGACTCCGCCTTTTGAT; SEQ. ID. NO. 202) for SEQ. ID. NO. 17 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 17 mRNA was evident in ovarian,renal, lung, colon, and breast cancer but weakly in CNS cancer;

FIG. 73 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 18in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1308 (ACATTCGCTTCTCCATCTGG; SEQ. ID. NO. 203) and OGS1309 (TGTCACGGAAGGGAACCAGG; SEQ. ID. NO. 204) for SEQ. ID. NO. 18 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 18 mRNA was evident in all cancertypes;

FIG. 74 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 19in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1069 (ACGCTGCCTCTGGGTCACTT; SEQ. ID. NO. 205) and OGS1070 (TTGGCAAATCAATGGCTTGTAAT; SEQ. ID. NO. 206) for SEQ. ID. NO. 19 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 19 mRNA was evident in all cancertypes;

FIG. 75 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 20in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1061 (ATGGCTTGGGTCATCAGGAC; SEQ. ID. NO. 207) and OGS1062 (GTGTCACTGGGCGTAAGATACTG; SEQ. ID. NO. 208) for SEQ. ID. NO. 20 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 20 mRNA was evident in all cancertypes but weakly in breast and colon cancer;

FIG. 76 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 21in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1097 (CACCAAATCAGCTGCTACTACTCC; SEQ. ID. NO. 209) andOGS 1098 (GATAAACCCCAAAGCAGAAAGATT; SEQ. ID. NO. 210) for SEQ. ID. NO.21 was used to perform RT-PCR. As indicated by the expected PCRamplicon, increased expression of SEQ. ID. NO. 21 mRNA was evident inall cancer types but weakly in leukemia;

FIG. 77 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 22in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1075 (CGAGATTCCGTGGGCGTAGG; SEQ. ID. NO. 211) and OGS1076 (TGAGTGGGAGCTTCGTAGG; SEQ. ID. NO. 212) for SEQ. ID. NO. 22 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 22 mRNA was evident in ovarian,lung, breast, and CNS cancer. Another larger transcript was weaklyexpressed in colon and renal cancer ion addition to melanoma;

FIG. 78 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 23in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1232 (TCAGAGTGGACGTTGGATTAC; SEQ. ID. NO. 213) and OGS1233 (TGCTTGAAATGTAGGAGAACA; SEQ. ID. NO. 214) for SEQ. ID. NO. 23 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 23 mRNA was evident in all cancertypes;

FIG. 79 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 24in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1067 (GAGGGGCATCAATCACACCGAGAA; SEQ. ID. NO. 215) andOGS 1068 (CCCCACCGCCCACCCATTTAGG; SEQ. ID. NO. 216) for SEQ. ID. NO. 24was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 24 mRNA was evident in ovarian,renal, lung, colon, breast cancer, and melanoma but weakly in CNS cancerand leukemia;

FIG. 80 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 25in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1099 (GGGGGCACCAGAGGCAGTAA; SEQ. ID. NO. 217) and OGS1100 (GGTTGTGGCGGGGGCAGTTGTG; SEQ. ID. NO. 218) for SEQ. ID. NO. 25 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 25 mRNA was evident in all cancertypes but weakly in leukemia;

FIG. 81 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 26in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1246 (ACAGACTCCTGTACTGCAAACC; SEQ. ID. NO. 219) and OGS1247 (TACCGGTTCGTCCTCTTCCTC; SEQ. ID. NO. 220) for SEQ. ID. NO. 26 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 26 mRNA was evident in all cancertypes;

FIG. 82 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 27in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1093 (GAAGTTCCTCACGCCCTGCTATC; SEQ. ID. NO. 221) andOGS 1094 (CTGGCTGGTGACCTGCTTTGAGTA; SEQ. ID. NO. 222) for SEQ. ID. NO.27 was used to perform RT-PCR. As indicated by the expected PCRamplicon, increased expression of SEQ. ID. NO. 27 mRNA was evident inall cancer types;

FIG. 83 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 28in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1332 (TAGGCGCGCCTGACATACAGCAATGCCAGTT; SEQ. ID. NO.223) and OGS 1333 (TAAGAATGCGGCCGCGCCACATCTTGAACACTTTGC; SEQ. ID. NO.224) for SEQ. ID. NO. 28 was used to perform RT-PCR. As indicated by theexpected PCR amplicon, increased expression of SEQ. ID. NO. 28 mRNA wasevident in ovarian, prostate, and renal cancer but weakly in all othertypes;

FIG. 84 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 29in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1101 (TGGGGAGGAGTTTGAGGAGCAGAC; SEQ. ID. NO. 225) andOGS 1102 (GTGGGACGGAGGGGGCAGTGAAG; SEQ. ID. NO. 226) for SEQ. ID. NO. 29was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 29 mRNA was evident in ovarian,renal, lung, colon, and breast cancer but weakly in CNS cancer andmelanoma;

FIG. 85 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 30in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1300 (GCAACTATTCGGAGCGCGTG; SEQ. ID. NO. 227) and OGS1301 (CCAGCAGCTTGTTGAGCTCC; SEQ. ID. NO. 228) for SEQ. ID. NO. 30 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 30 mRNA was evident in all cancertypes;

FIG. 86 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 31in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1302 (GGAGGAGCTAAGCGTCATCGC; SEQ. ID. NO. 229) and OGS1303 (TCGCTTCAGCGCGTAGACC; SEQ. ID. NO. 230) for SEQ. ID. NO. 31 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 31 mRNA was evident in all cancertypes;

FIG. 87 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 32in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1077 (GCGTCCGGGCCTGTCTTCAACCT; SEQ. ID. NO. 153) andOGS 1078 (GCCCCACCCTCTACCCCACCACTA; SEQ. ID. NO. 154) for SEQ. ID. NO.32 was used to perform RT-PCR. As indicated by the expected PCRamplicon, increased expression of SEQ. ID. NO. 32 mRNA was evident inovarian cancer and melanoma but weaker expression was detectable in CNS,breast, colon, lung, and renal cancer;

FIG. 88 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 33in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1292 (TATTAGTTGGGATGGTGGTAGCAC; SEQ. ID. NO. 231) andOGS 1294 (GAGAATTCGAGTCGACGATGAC; SEQ. ID. NO. 232) for SEQ. ID. NO. 33was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 33 mRNA was evident only in ovariancancer samples;

FIG. 89 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 34in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1242 (GAAATTGTGTTGACGCAGTCTCC; SEQ. ID. NO. 233) andOGS 1243 (AGGCACACAACAGAGGCAGTTC; SEQ. ID. NO. 234) for SEQ. ID. NO. 34was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 34 mRNA was evident only in ovariancancer samples;

FIG. 90 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 35in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1141 (GAGATCCTGATCAAGGTGCAGG; SEQ. ID. NO. 155) and OGS1142 (TGCACGCTCACAGCAGTCAGG; SEQ. ID. NO. 156) for SEQ. ID. NO. 35 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 35 mRNA was evident in ovarian,lung and breast cancer, but weakly in colon and CNS cancer;

FIG. 91 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 36in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1280 (GTACATCAACCTCCTGCTGTCC; SEQ. ID. NO. 235) and OGS1281 (GACATCTCCAAGTCCCAGCATG; SEQ. ID. NO. 236) for SEQ. ID. NO. 36 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 36 mRNA was evident in all cancertypes;

FIG. 92 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 37in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1159 (AGTCTCTCACTGTGCCTTATGCC; SEQ. ID. NO. 237) andOGS 1160 (AGTCCTAAGAACTGTAAACG; SEQ. ID. NO. 238) for SEQ. ID. NO. 37was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 37 mRNA was evident only in ovarianand renal cancer;

FIG. 93 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 38in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1202 (AACATGACTAAGATGCCCAACC; SEQ. ID. NO. 157) and OGS1203 (AATCTCCTTCACCTCCACTACTG; SEQ. ID. NO. 158) for SEQ. ID. NO. 38 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 38 mRNA was evident in all cancertypes;

FIG. 94 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 39in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1310 (CATCTATACGTGGATTGAGGA; SEQ. ID. NO. 239) and OGS1311 (ATAGGTACCAGGTATGAGCTG; SEQ. ID. NO. 240) for SEQ. ID. NO. 39 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 39 mRNA was evident in all cancertypes;

FIG. 95 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 40in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1155 (TGTCCACATCATCATCGTCATCC; SEQ. ID. NO. 241) andOGS 1156 (TGTCACTGGTCGGTCGCTGAGG; SEQ. ID. NO. 242) for SEQ. ID. NO. 39was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 39 mRNA was evident in all cancertypes;

FIG. 96 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 41in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1212 (AAGCATAGCCATAGGTGATTGG; SEQ. ID. NO. 159) and OGS1213 (ACAGGTATCAGACAAGGGAGCAG; SEQ. ID. NO. 160) for SEQ. ID. NO. 41 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 41 mRNA was evident only in ovarianand renal cancer and leukemia;

FIG. 97 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 42in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1316 (CATGGGGCTTAAGATGTC; SEQ. ID. NO. 243) and OGS1317 (GTCGATTTCTCCATCATCTG; SEQ. ID. NO. 244) for SEQ. ID. NO. 42 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 42 mRNA was evident in all cancertypes;

FIG. 98 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 43in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1306 (AAGAGGCGCTCTACTAGCCG; SEQ. ID. NO. 245) and OGS1307 (CTTTCCACATGGAACACAGG; SEQ. ID. NO. 246) for SEQ. ID. NO. 43 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 43 mRNA was evident in all cancertypes;

FIG. 99 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 44in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1171 (TTACGACCTATTTCTCCGTGG; SEQ. ID. NO. 161) and OGS1172 (AATGCAATAATTGGCCACTGC; SEQ. ID. NO. 162) for SEQ. ID. NO. 44 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 44 mRNA was evident in all cancertypes;

FIG. 100 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 45in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1175 (ACACATCAAACTGCTTATCCAGG; SEQ. ID. NO. 163) andOGS 1176 (ACTGATGTGAAAATGCACATCC; SEQ. ID. NO. 164) for SEQ. ID. NO. 45was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 45 mRNA was evident only in ovariancancer samples;

FIG. 101 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 46in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1286 (CATTTTCCTGGAATTTGATACAG; SEQ. ID. NO. 247) andOGS 1287 (GTAGAGAGTTTATTTGGGCCAAG; SEQ. ID. NO. 248) for SEQ. ID. NO. 46was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 46 mRNA was evident in all cancertypes;

FIG. 102 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 47in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1244 (CATCTATGGTAACTACAATCG; SEQ. ID. NO. 249) and OGS1245 (GTAGAAGTCACTGATCAGACAC; SEQ. ID. NO. 250) for SEQ. ID. NO. 47 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 47 mRNA was evident only in ovariancancer;

FIG. 103 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 48in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1282 (ATGGCTCATACAGCACTCAGG; SEQ. ID. NO. 165) and OGS1283 (GAACTGTCACTCCGGAAAGCCT; SEQ. ID. NO. 166) for SEQ. ID. NO. 48 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 48 mRNA was evident in all cancertypes;

FIG. 104 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 50in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1035 (CTGCCTGCCAACCTTTCCATTTCT; SEQ. ID. NO. 251) andOGS 1036 (TGAGCAGCCACAGCAGCATTAGG; SEQ. ID. NO. 252) for SEQ. ID. NO. 50was used to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 50 mRNA was evident in all cancertypes but weak in CNS cancer and leukemia, and;

FIG. 105 is a picture of RT-PCR data showing the differential expressiondata for the STAR selected ovarian cancer-related human SEQ. ID. NO. 169in RNA samples derived from the NCI-60 panel of cancer cell lines. Aprimer pair, OGS 1248 (CACCTGATCAGGTGGATAAGG; SEQ. ID. NO. 253) and OGS1249 (TCCCAGGTAGAAGGTGGAATCC; SEQ. ID. NO. 254) for SEQ. ID. NO. 169 wasused to perform RT-PCR. As indicated by the expected PCR amplicon,increased expression of SEQ. ID. NO. 169 mRNA was evident in ovarian,renal, and lung cancer but weak in CNS cancer.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The applicant employed a carefully planned strategy to identify andisolate genetic sequences involved in ovarian cancer. The processinvolved the following steps: 1) preparation of highly representativecDNA libraries using mRNA isolated from LMPs and malignant ovariancancer samples of human origin; 2) isolation of sequences upregulated inthe malignant ovarian cancer samples; 3) identification andcharacterization of upregulated sequences; 4) selection of upregulatedsequences for tissue specificity; 5) determination of knock-down effectson ovarian cancer cell line proliferation and migration; and 6)determination of the expression pattern of each upregulated sequence insamples derived from nine different cancer types. The results discussedin this disclosure demonstrate the advantage of targeting ovariancancer-related genes that are highly specific to this differentiatedcell type compared to normal tissues and provide a more efficientscreening method when studying the genetic basis of diseases anddisorders. Polynucleotide and/or polypeptide sequences that are knownbut have not had a role assigned to them until the present disclosurehave also been isolated and shown to have a critical role in ovariancancer cell line proliferation and migration. Finally, novelpolynucleotide and/or polypeptide sequences have been identified thatplay a role as well.

The present invention is illustrated in further details below in anon-limiting fashion.

A—Material and Methods

Commercially available reagents referred to in the present disclosurewere used according to supplier's instructions unless otherwiseindicated. Throughout the present disclosure certain starting materialswere prepared as follows:

B—Preparation of LMP and Malignant Ovarian Cancer Cells

LMP and malignant ovarian tumor samples were selected based onhistopathology to identify the respective stage and grade (Table B). LMPwas chosen instead of normal ovarian tissue to avoid genes thatassociated with proliferation due to ovulation. Also very few cellswould have been recovered and stromal cells would have been a majorcontaminant. LMP and serous (most common) ovarian tumors represent theextremes of tumorigenicity, differentiation and invasion. Once thesample were selected, total RNA was extracted with Trizol™ (InVitrogen,Grand Island, N.Y.) after the tissues were homogenized. The quality ofthe RNA was assessed using a 2100 Bioanalyzer (Agilent Technologies,Palo Alto, Calif.)

TABLE B shows the pathologies including grade and stage of the differentovarian cancer samples used on the macroarrays. MF Position Code on No.Pathologies Symbol Stage Grade Macroarray 15 Borderline serous B 1b B A116 Borderline serous B 2a B B1 17 Borderline/carcinoma B/CS 3c 1 F1serous 18 Borderline serous B 3c B C1 19 Borderline serous B 1b B D1 20Borderline serous B 1a B E1 42 Carcinoma serous of the CSS 3a 3 A4surface 22 Carcinoma serous CS 1b 3 A2 30 Carcinoma serous CS 2c 3 E2 23Carcinoma serous CS 3c 3 F2 25 Carcinoma serous CS 3c 3 B2 26 Carcinomaserous CS 3c 3 A3 27 Carcinoma serous CS 3c 3 C2 28 Carcinoma serous CS3c 3 D2 43 Carcinoma serous CS 3c 3 B4 45 Carcinoma serous CS 3c 3 D4 49Carcinoma serous CS 3c 2 F4 41 Carcinoma endo- CE 3b 3 G3 metrioide 40Carcinoma endo- CE 3c 3 F3 metrioide 44 Carcinoma endo- CE 3c 3 C4metrioide 39 Carcinoma endo- CE 3c 2 E3 metrioide 50 Carcinoma endo- CE1c 1 G4 metrioide 46 Carcinoma endo- CE 1a 2 E4 metrioide 34 Clear cellcarcinoma CCC 3c 2 B3 38 Clear cell carcinoma CCC 3c 3 D3 37 Clear cellcarcinoma CCC 1c 2 C3C—Method of Isolating Differentially Expressed mRNA

Key to the discovery of differentially expressed sequences unique tomalignant ovarian cancer is the use of the applicant's patented STARtechnology (Subtractive Transcription-based Amplification of mRNA; U.S.Pat. No. 5,712,127 Malek et al., 1998). Based on this procedure, mRNAisolated from malignant ovarian tumor sample is used to prepare “testerRNA”, which is hybridized to complementary single-stranded “driver DNA”prepared from mRNA from LMP sample and only the un-hybridized “testerRNA” is recovered, and used to create cloned cDNA libraries, termed“subtracted libraries”. Thus, the “subtracted libraries” are enrichedfor differentially expressed sequences inclusive of rare and novel mRNAsoften missed by micro-array hybridization analysis. These rare and novelmRNA are thought to be representative of important gene targets for thedevelopment of better diagnostic and therapeutic strategies.

The clones contained in the enriched “subtracted libraries” areidentified by DNA sequence analysis and their potential functionassessed by acquiring information available in public databases (NCBIand GeneCard). The non-redundant clones are then used to prepare DNAmicro-arrays, which are used to quantify their relative differentialexpression patterns by hybridization to fluorescent cDNA probes. Twoclasses of cDNA probes may be used, those which are generated fromeither RNA transcripts prepared from the same subtracted libraries(subtracted probes) or from mRNA isolated from different ovarian LMP andmalignant samples (standard probes). The use of subtracted probesprovides increased sensitivity for detecting the low abundance mRNAsequences that are preserved and enriched by STAR. Furthermore, thespecificity of the differentially expressed sequences to malignantovarian cancer is measured by hybridizing radio-labeled probes preparedfrom each selected sequence to macroarrays containing RNA from differentLMP and malignant ovarian cancer samples and different normal humantissues.

A major challenge in gene expression profiling is the limited quantitiesof RNA available for molecular analysis. The amount of RNA isolated frommany human specimens (needle aspiration, laser capture micro-dissection(LCM) samples and transfected cultured cells) is often insufficient forpreparing: 1) conventional tester and driver materials for STAR; 2)standard cDNA probes for DNA micro-array analysis; 3) RNA macroarraysfor testing the specificity of expression; 4) Northern blots and; 5)full-length cDNA clones for further biological validation andcharacterization etc. Thus, the applicant has developed a proprietarytechnology called RAMP (RNA Amplification Procedure) (U.S. patentapplication Ser. No. 11/000,958 published under No. US 2005/0153333A1 onJul. 14, 2005 and entitled “Selective Terminal Tagging of NucleicAcids”), which linearly amplifies the mRNA contained in total RNAsamples yielding microgram quantities of amplified RNA sufficient forthe various analytical applications. The RAMP RNA produced is largelyfull-length mRNA-like sequences as a result of the proprietary methodfor adding a terminal sequence tag to the 3′-ends of single-strandedcDNA molecules, for use in linear transcription amplification. Greaterthan 99.5% of the sequences amplified in RAMP reactions show <2-foldvariability and thus, RAMP provides unbiased RNA samples in quantitiessufficient to enable the discovery of the unique mRNA sequences involvedin ovarian cancer.

D—Preparation of Human Malignant Ovarian Cancer Subtracted Library

Total RNA from five human ovarian LMP samples (MF-15, -16, -18, -19 and-20) (Table B) and five malignant ovarian cancer samples (MF-22, -25,-27, -28 and -30) (Table B) (CHUM, Montreal, QC) were prepared asdescribed above. Following a slight modification of the teachings ofMalek et al., 1998 (U.S. Pat. No. 5,712,127) i.e., preparation of thecDNA libraries on the paramagnetic beads as described below), 1 μg oftotal RNA from each sample were used to prepare highly representativecDNA libraries on streptavidin-coated paramagnetic beads (InVitrogen,Grand Island, N.Y.) for preparing tester and driver materials. In eachcase, first-strand cDNA was synthesized using an oligo dT₁₁ primer with3′ locking nucleotides (e.g., A, G or C), a 5′-biotin moiety andcontaining a Not I recognition site (OGS 364: SEQ. ID. NO. 90) Next,second-strand cDNA synthesis was performed according to themanufacturer's procedure for double-stranded cDNA synthesis (Invitrogen,Burlington, ON) and the resulting double-stranded cDNA ligated tolinkers containing an Asc I recognition site (New England Biolabs,Pickering, ON). The double-stranded cDNAs were then digested with Asc Iand Not I restriction enzymes (New England Biolabs, Pickering, ON),purified from the excess linkers using the cDNA fractionation columnfrom Invitrogen (Burlington, ON) as specified by the manufacturer. Eachsample was equally divided and ligated separately to specializedoligonucleotide promoter tags, TAG1 (OGS 594 and 595: SEQ. ID. NO: 91and SEQ. ID. NO:92) and TAG2 (OGS458 and 459: SEQ. ID. NO:93 and SEQ.ID. NO:94) used for preparing tester and driver materials, respectively.Thereafter, each ligated cDNA was purified by capturing on thestreptavidin beads as described by the supplier (InVitrogen, GrandIsland, N.Y.), and transcribed in vitro with T7 RNA polymerase (Ambion,Austin, Tex.).

Next, in order to prepare 3′-represented tester and driver libraries, a10-μg aliquot of each of the in vitro synthesized RNA was converted todouble-stranded cDNA by performing first-strand cDNA synthesis asdescribed above followed by primer-directed (primer OGS 494 (SEQ. ID.NO:95) for TAG1 and primer OGS 302 (SEQ. ID. NO:96) for TAG2)second-strand DNA synthesis using Advantage-2 Taq polymerase (BDBiosciences Clontech, Mississauga, ON). The double-stranded cDNA waspurified using Qiaquick columns and quantified at A_(260 nm).Thereafter, 6×1-μg aliquots of each double-stranded cDNA was digestedindividually with one of the following 4-base recognition restrictionenzymes Rsa 1, Sau3A1, Mse 1, Msp 1, HinPI 1 and Bsh 1236I (MBIFermentas, Burlington, ON), yielding up to six possible 3′-fragments foreach RNA species contained in the cDNA library. Following digestion, therestriction enzymes were inactivated with phenol and the set of sixreactions pooled. The restriction enzymes sites were then blunted withT4 DNA polymerase and ligated to linkers containing an Asc 1 recognitionsite. Each linker-adapted pooled DNA sample was digested with Asc 1 andNot 1 restriction enzymes, desalted and ligated to specializedoligonucleotide promoter tags, TAG1 (OGS 594 and 595) for the originalTAG1-derived materials to generate tester RNA and TAG2-related OGS 621and 622 (SEQ. ID. NO:97 and SEQ. ID. NO:98) with only the promotersequence for the original TAG2-derived materials for generating driverDNA. The promoter-ligated materials were purified using the streptavidinbeads, which were then transcribed in vitro with either T7 RNApolymerase (Ambion, Austin, Tex.), purified and quantified atA_(260 nm). The resulting TAG1 3′-represented RNA was used directly as“tester RNA” whereas, the TAG2 3′-represented RNA was used to synthesizefirst-strand cDNA, which then served as single-stranded “driver DNA”.Each “driver DNA” reaction was treated with RNase A and RNase H toremove the RNA, phenol extracted and purified before use. An equivalentamount of each driver RNA for the five LMP samples were pooled beforesynthesis of the single-stranded driver DNA.

The following 3′-represented libraries were prepared:

Tester 1 (MF-22)—human malignant ovarian cancer donor 1

Tester 2 (MF-25)—human malignant ovarian cancer donor 2

Tester 3 (MF-27)—human malignant ovarian cancer donor 3

Tester 4 (MF-28)—human malignant ovarian cancer donor 4

Tester 5 (MF-30)—human malignant ovarian cancer donor 5

Driver 1 (MF-15)—human ovarian LMP donor 1

Driver 2 (MF-16)—human ovarian LMP donor 2

Driver 3 (MF-18)—human ovarian LMP donor 3

Driver 4 (MF-19)—human ovarian LMP donor 4

Driver 5 (MF-20)—human ovarian LMP donor 5

Each tester RNA sample was subtracted following the teachings of U.S.Pat. No. 5,712,127 with the pooled driver DNA (MF-15, -16, -18, -19 and-20) in a ratio of 1:100 for 2-rounds following the teachings of Maleket al., 1998 (U.S. Pat. No. 5,712,127). Additionally, control reactionscontaining tester RNA and no driver DNA, and tester RNA plus driver DNAbut no RNase H were prepared. The tester RNA remaining in each reactionafter subtraction was converted to double-stranded DNA, and a volume of5% removed and amplified in a standard PCR reaction for 30-cycles foranalytical purposes. The remaining 95% of only the tester-driver plusRNase H subtracted samples after 2-rounds were amplified for 4-cycles inPCR, digested with Asc I and Not I restriction enzymes, and one halfligated into the pCATRMAN (SEQ. ID. NO:99) plasmid vector and the otherhalf, into the p20 (SEQ. ID. NO:100) plasmid vector. The ligatedmaterials were transformed into E. coli DH10B and individual clonescontained in the pCATRMAN libraries were picked for further analysis(DNA sequencing and hybridization) whereas, clones contained in each p20library were pooled for use as subtracted probes. Each 4-cyclesamplified cloned subtracted library contained between 15,000 and 25,000colonies. Additionally, in order to prepare subtracted cDNA probes,reciprocal subtraction for 2-rounds was performed using instead, thepooled driver RNA as “tester” and each of the malignant tester RNA as“driver”. The materials remaining after subtraction for each weresimilarly amplified for 4-cycles in PCR, digested with Asc I and Not Irestriction enzymes, and one half ligated into the p20 plasmid vector.

The following cloned subtracted libraries were prepared:

SL123—Tester 1 (MF-22) minus Pooled Driver (MF-15, -16, -18, -19 and-20)SL124—Tester 2 (MF-25) minus Pooled Driver (MF-15, -16, -18, -19 and-20)SL125—Tester 3 (MF-27) minus Pooled Driver (MF-15, -16, -18, -19 and-20)SL126—Tester 4 (MF-28) minus Pooled Driver (MF-15, -16, -18, -19 and-20)SL127—Tester 5 (MF-30) minus Pooled Driver (MF-15, -16, -18, -19 and-20)SL133—Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 1(MF-22)SL134—Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 2(MF-25)SL135—Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 3(MF-27)SL136—Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 4(MF-28)SL137—Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 5(MF-30)

A 5-μL aliquot of the 30-cycles PCR amplified subtracted andnon-subtracted materials were visualized on a 1.5% agarose gelcontaining ethidium bromide and then transferred to Hybond N+(AmershamBiosciences, Piscataway, N.J.) nylon membrane for Southern blotanalysis. Using radiolabeled probes specific for GAPDH(glyceraldehyde-3-phosphate dehydrogenase; Accession #M32599.1) andβ-actin (Accession #X00351), which are typically non-differentiallyexpressed house-keeping genes, it was evident that there was subtractionof both GAPDH and β-actin (FIG. 51, Panels A and B). Yet, at the sametime, a probe specific for CCNE1 (Accession #NM_001238, a gene known tobe upregulated in malignant ovarian cancer, indicated that it was notsubtracted (FIG. 51, Panel C). Based on these results, it wasanticipated that the subtracted libraries would be enriched fordifferentially expressed upregulated sequences.

E—Sequence Identification and Annotation of Clones Contained in theSubtracted Libraries:

Approximately ˜5300 individual colonies contained in the pCATRMANsubtracted libraries (SL123 to SL127) described above were randomlypicked using a Qbot (Genetix Inc., Boston, Mass.) into 60 μL ofautoclaved water. Then, 42 μL of each was used in a 100-μL standard PCRreaction containing oligonucleotide primers, OGS 1 and OGS 142 andamplified for 40-cycles (94° C. for 10 minutes, 40× (94° C. for 40seconds, 55° C. for 30 seconds and 72° C. for 2 minutes) followed by 72°C. for 7 minutes) in 96-wells microtitre plates using HotStart™ Taqpolymerase (Qiagen, Mississauga, ON). The completed PCR reactions weredesalted using the 96-well filter plates (Corning) and the ampliconsrecovered in 100 μL 10 mM Tris (pH 8.0). A 5-μL aliquot of each PCRreaction was visualized on a 1.5% agarose gel containing ethidiumbromide and only those reactions containing a single amplified productwere selected for DNA sequence analysis using standard DNA sequencingperformed on an ABI 3100 instrument (Applied Biosystems, Foster City,Calif.). Each DNA sequence obtained was given a Sequence IdentificationNumber and entered into a database for subsequent tracking andannotation.

Each sequence was selected for BLAST analysis of public databases (e.g.NCBI). Absent from these sequences were the standard housekeeping genes(GAPDH, actin, most ribosomal proteins etc.), which was a goodindication that the subtracted library was depleted of at least therelatively abundant non-differentially expressed sequences.

Once sequencing and annotation of the selected clones were completed,the next step involved identifying those sequences that were actuallyupregulated in the malignant ovarian cancer samples compared to the LMPsamples.

F—Hybridization Analysis for Identifying Upregulated Sequences

The PCR amplicons representing the annotated sequences from the pCATRMANlibraries described above were used to prepare DNA microarrays. Thepurified PCR amplicons contained in 70 μL of the PCR reactions preparedin the previous section was lyophilized and each reconstituted in 20 μLof spotting solution comprising 3×SSC and 0.1% sarkosyl. DNAmicro-arrays of each amplicon in triplicate were then prepared usingCMT-GAP2 slides (Corning, Corning, N.Y.) and the GMS 417 spotter(Affymetrix, Santa Clara, Calif.).

The DNA micro-arrays were then hybridized with either standard orsubtracted cy3 and cy5 labelled cDNA probes as recommended by thesupplier (Amersham Biosciences, Piscataway, N.J.). The standard cDNAprobes were synthesized using RAMP amplified RNA prepared from thedifferent human ovarian LMP and malignant samples. It is well known tothe skilled artisan that standard cDNA probes only provide limitedsensitivity of detection and consequently, low abundance sequencescontained in the cDNA probes are usually missed. Thus, the hybridizationanalysis was also performed using cy3 and cy5 labelled subtracted cDNAprobes prepared from in vitro transcribed RNA generated from subtractedlibraries (SLP123 to SLP127 and SLP133 to SLP137) cloned into the p20plasmid vector and represent the different tester and driver materials.These subtracted libraries may be enriched for low abundance sequencesas a result of following the teachings of Malek et al., 1998 (U.S. Pat.No. 5,712,127), and therefore, may provide increased detectionsensitivity.

All hybridization reactions were performed using the dye-swap procedureas recommended by the supplier (Amersham Biosciences, Piscataway, N.J.)and approximately 750 putatively differentially expressed upregulated(>2-fold) sequences were selected for further analysis.

G—Determining Malignant Ovarian Cancer Specificity of the DifferentiallyExpressed Sequences Identified:

The differentially expressed sequences identified in Section F for thedifferent human malignant ovarian cancer subtracted libraries (SL123 toSL127) were tested for specificity by hybridization to nylonmembrane-based macroarrays. The macroarrays were prepared using RAMPamplified RNA from 6 LMP and 20 malignant human ovarian samples, and 30normal human tissues (adrenal, liver, lung, ovary, skeletal muscle,heart, cervix, thyroid, breast, placenta, adrenal cortex, kidney, venacava, fallopian tube, pancreas, testicle, jejunum, aorta, esophagus,prostate, stomach, spleen, ileum, trachea, brain, colon, thymus, smallintestine, bladder and duodenum) purchased commercially (Ambion, Austin,Tex.). In addition, RAMP RNA prepared from breast cancer cell lines, MDAand MCF7, prostate cancer cell line, LNCap, and a normal and prostatecancer LCM microdissected sample. Because of the limited quantities ofmRNA available for many of these samples, it was necessary to firstamplify the mRNA using the RAMP methodology. Each amplified RNA samplewas reconstituted to a final concentration of 250 ng/μL in 3×SSC and0.1% sarkosyl in a 96-well microtitre plate and 1 μL spotted onto HybondN+ nylon membranes using the specialized MULTI-PRINT™ apparatus (VPScientific, San Diego, Calif.), air dried and UV-cross linked. Of the˜750 different sequences selected from SL123 to SL127 for macroarrayanalysis, only 250 sequences were individually radiolabeled withα-³²P-dCTP using the random priming procedure recommended by thesupplier (Amersham, Piscataway, N.J.) and used as probes on themacroarrays thus far. Hybridization and washing steps were performedfollowing standard procedures well known to those skilled in the art.

Occasionally, the results obtained from the macroarray methodology wereinconclusive. For example, probing the membranes with certain STARclones resulted in patterns where all the RNA samples appeared toexpress equal levels of the message or in patterns where there was nosignal. This suggested that not all STAR clones were useful tools toverify the expression of their respective genes. To circumvent thisproblem, RT-PCR was used to determine the specificity of expression.Using the same RAMP RNA samples that were spotted on the macroarrays,500 μg of RNA was converted to single-stranded cDNA with Thermoscript RT(Invitrogen, Burlington, ON) as described by the manufacturer. The cDNAreaction was diluted so that 1/200 of the reaction was used for each PCRexperiment. After trial PCR reactions with gene-specific primersdesigned against each SEQ. ID NOs. to be tested, the linear range of thereaction was determined and applied to all samples, PCR was conducted in96-well plates using Hot-Start Taq Polymerase from Qiagen (Mississauga,ON) in a DNA Engine Tetrad from MJ Research. Half of the reactionmixture was loaded on a 1.2% agarose/ethidium bromide gel and theamplicons visualized with UV light.

Of the 250 sequences tested, approximately 55% were found to beupregulated in many of the malignant samples compared to the LMPs.However, many of these sequences were also readily detected in amajority of the different normal human tissues. Based on these results,those sequences that were detected in many of the other human tissues atsignificantly elevated levels were eliminated. Consequently, only 49sequences, which appeared to be upregulated and highly malignant ovariancancer-specific, were selected for biological validation studies. Thissubset of 49 sequences include some genes previously reported in theliterature to be upregulated in ovarian cancer but without demonstrationof their relative expression in normal tissues. The macroarray data forFOLR1 (SEQ. ID. NO. 50) is included to exemplify the hybridizationpattern and specificity of a gene that is already known to be involvedin the development of ovarian cancer.

FIGS. 1-49 and 51 show the macroarray hybridization signal patterns andRT-PCR amplification data for the malignant ovarian cancer and normalhuman tissues relative to LMPs for the 50 sequences isolated andselected for biological validation. Amongst the 50 selected sequences,27 were associated with genes having functional annotation 15 wereassociated with genes with no functional annotation and 8 were novelsequences (genomic hits). The identification of gene products involvedin regulating the development of ovarian cancer has thus led to thediscovery of highly specific, including novel targets, for thedevelopment of new therapeutic strategies for ovarian cancer management.Representative sequences summarized in Table 2 are presented below andcorresponding sequences are illustrated in Table 4.

The present invention thus relates in one aspect thereof to a method ofrepresentatively identifying a differentially expressed sequenceinvolved in ovarian cancer. The sequence may be, for example,differentially expressed in a malignant ovarian cancer cell compared toa LMP ovarian cancer cell or normal ovarian cells. The sequence may be,for example, differentially expressed in a malignant ovarian cancer celland a LMP ovarian cancer cell compared to a normal ovarian cell.

The method of the present invention may comprise the following steps orsome of the following steps;

-   -   a) separately providing total messenger RNA from malignant and        LMP ovarian cancer cells, and normal ovarian cells, the total        messenger RNA may comprise, for example, at least one        endogenously differentially expressed sequence,    -   b) generating (e.g., single copy) of a) single-stranded cDNA        from each messenger RNA of malignant ovarian cancer cell and        (e.g., randomly) tagging the 3′-end of the single-stranded cDNA        with a RNA polymerase promoter sequence and a first sequence        tag;    -   c) generating (e.g., single copy) of a) single-stranded cDNA        from each messenger RNA of LMP ovarian cancer cells or normal        ovarian cell and (e.g., randomly) tagging the 3′-end of the        single-stranded cDNA with a RNA polymerase promoter sequence and        a second sequence tag;    -   d) separately generating partially or completely double-stranded        5′-tagged-DNA from each of b) and c), the double-stranded        5′-tagged-DNA may thus comprise in a 5′ to 3′ direction, a        double-stranded RNA polymerase promoter, a first or second        sequence tag and an expressed nucleic acid sequence,    -   e) separately linearly amplifying a first and second tagged        sense RNA from each of d) with a RNA polymerase enzyme (which        may be selected based on the promoter used for tagging),    -   f) generating single-stranded complementary first or second        tagged DNA from one of e),    -   g) hybridizing the single-stranded complementary first or second        tagged DNA of f) with the other linearly amplified sense RNA of        e),    -   h) recovering unhybridized RNA with the help of the first or        second sequence tag (for example by PCR or hybridization), and;    -   i) identifying (determining) the nucleotide sequence of        unhybridized RNA. The method may further comprise the step of        comparatively determining the presence of the identified        differentially expressed sequence in a cancer cell relative to a        normal cell (e.g., a normal ovarian cell, a normal prostate        cell, a normal breast cell etc.) or relative to a standard        value.

The method may be used to preferentially identify a sequence which isupregulated in malignant ovarian cancer cell compared to a cell from alow malignancy potential ovarian cancer and/or compared to a normalcell.

In accordance with the present invention, a sequence may be furtherselected based on a reduced, lowered or substantially absent expressionin a subset of other normal cell (e.g., a normal ovarian cell) ortissue, therefore representing a candidate sequence specificallyinvolved in ovarian cancer.

The method may also further comprise a step of determining the completesequence of the nucleotide sequence and may also comprise determiningthe coding sequence of the nucleotide sequence.

A sequence may also be selected for its specificity to other types oftumor cells, thus identifying a sequence having a more generalizedinvolvement in the development of cancer. These types of sequence maytherefore represent desirable candidates having a more universal utilityin the treatment and/or detection of cancer.

The present invention also relates in a further aspect, to the isolateddifferentially expressed sequence (polynucleotide and polypeptide)identified by the method of the present invention.

SEQ. ID. NO:1:

The candidate STAR sequence for SEQ. ID. NO:1 maps to a genomic hit andest hits according to NCBI's nr and est databases (see Table 2).Although, the matching ests are clustered into a new Unigene identifiernumber, Hs.555871, the STAR sequence does not map to any of the knownmRNA sequences listed in this cluster, which codes for guaninenucleotide binding protein (G protein), gamma transducing activitypolypeptide 1 (GNGT1). We have demonstrated that this STAR clonesequence is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 1), which have not been previously reported. Thus, it is believedthat the gene comprising this STAR sequence or a related gene member asis outlined in the Unigene cluster may be required for ovarian cancertumorigenesis.

SEQ. ID. NO:2:

The candidate protein encoded by the isolated SEQ. ID. NO:2 isassociated with a previously identified gene that encodes a predictedpolypeptide, interferon-induced protein 44-like (IFI44L) with an unknownfunction (see Table 2). We have demonstrated that expression of thisgene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 2), which have not been previously reported. Thus, it is believedthat expression of this gene may be required for or involved for ovariancancer tumorigenesis.

SEQ. ID. NO:3:

The candidate protein encoded by the isolated SEQ. ID. NO:3 isassociated with a previously identified gene that encodes a knownpolypeptide, HOX D1, which contains a homeobox DNA-binding domain. Thisgene is a member of the Antp homeobox family and is nuclearsequence-specific transcription factor that is previously known to beinvolved in differentiation and limb development (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and thenormal human tissues (FIG. 3), which have not been previously reported.Thus, it is believed that the gene may be required for, or involved inovarian cancer tumorigenesis as well.

SEQ. ID. NO:4:

The candidate protein encoded by the isolated SEQ. ID. NO:4 isassociated with a previously identified gene that encodes a hypotheticalpolypeptide, LOC92196, similar to death-associated protein with anunknown function (see Table 2). We have demonstrated that expression ofthis gene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 4), which have not been previously reported. Thus, it is believedthat expression of this gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:5

The candidate protein encoded by the isolated SEQ. ID. NO:5 isassociated with a previously identified gene that encodes a predictedpolypeptide, interferon-induced protein with tetratricopeptide repeats 1(IFIT1), with unknown function (see Table 2). We have demonstrated thatexpression of this gene is markedly upregulated in malignant ovariancancer samples compared to ovarian LMP samples and a majority of normalhuman tissues (FIG. 5), which have not been previously reported. Thus,it is believed that expression of this gene may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:6:

The candidate protein encoded by the isolated SEQ. ID. NO:6 isassociated with a previously identified gene that encodes a knownprotein, glycine dehydrogenase (GLDC) (decarboxylating; glycinedecarboxylase, glycine cleavage system protein P), which is amitochondrial enzyme that catalyzes the degradation of glycine (seeTable 2). We have demonstrated that expression of this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 6), which have notbeen previously reported. Thus, it is believed that expression of thisgene may be required for, or involved in ovarian cancer tumorigenesis.The GLDC activity may be detected, for example, by measuring thedegradation of glycine into urea.

SEQ. ID. NO:7:

The candidate protein encoded by the isolated SEQ. ID. NO:7 isassociated with a previously identified gene that encodes a protein,dipeptidase 3 (DPEP3), which has membrane dipeptidase (proteolysis andpeptidolysis) activity (see Table 2). We have demonstrated thatexpression of this gene is markedly upregulated in malignant ovariancancer samples compared to ovarian LMP samples and a majority of normalhuman tissues (FIG. 7), which have not been previously reported. Thus,it is believed that expression of this gene may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:8

The candidate protein encoded by the isolated SEQ. ID. NO:8 isassociated with a previously identified gene that encodes a protein,neuromedin U (NMU), which is a neuropeptide with potent activity onsmooth muscle (see Table 2). We have demonstrated that expression ofthis gene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 8), which have not been previously reported. Thus, it is believedthat expression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:9

The candidate protein encoded by the isolated SEQ. ID. NO:9 isassociated with a previously identified gene that encodes a protein,bone morphogenetic protein 7 (BMP7), which plays a role in calciumregulation and bone homeostasis (see Table 2). We have demonstrated thatexpression of this gene is markedly upregulated in malignant ovariancancer samples compared to ovarian LMP samples and a majority of normalhuman tissues (FIG. 9), which have not been previously reported. Thus,it is believed that expression of the gene may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:10

The candidate protein encoded by the isolated SEQ. ID. NO:10 isassociated with a previously identified gene that encodes a protein,cyclin-dependent kinase inhibitor 3 (CDKN3) (CDK2-associated dualspecificity phosphatase), which is expressed at the G1 to S transitionof the cell cycle (see Table 2). We have demonstrated that expression ofthis gene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 10), which have not been previously reported. Thus, it is believedthat expression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:11

The candidate protein encoded by the isolated SEQ. ID. NO:11 isassociated with a previously identified gene that encodes a protein,CDC28 protein kinase regulatory subunit 1B (CKS1B), which hascyclin-dependent protein kinase activity in cell cycle regulation (seeTable 2). We have demonstrated that expression of this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 11), which have notbeen previously reported. Thus, it is believed that expression of thegene may be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:12

The candidate protein encoded by the isolated SEQ. ID. NO:12 isassociated with a previously identified gene that encodes a protein,preferentially expressed antigen in melanoma (PRAME), which has no knownfunction (see Table 2). We have demonstrated that expression of thisgene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 12), which have not been previously reported. Thus, it is believedthat expression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:13

The candidate protein encoded by the isolated SEQ. ID. NO:13 isassociated with a previously identified gene that encodes a protein,ISG15 ubiquitin-like modifier (ISG15), which is associated withubiquitin-dependent protein catabolism (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 13), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:14

The candidate STAR sequence represented by the isolated SEQ. ID. NO:14is associated with a previously identified partial gene sequence relatedto Accession #AI922121.1 (see Table 2), which codes for a yet unknownprotein. We have demonstrated that this STAR clone sequence is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 14), which have notbeen previously reported. Thus, it is believed that expression of thegene corresponding to this STAR sequence (and polynucleotide sequencescomprising the STAR sequence) may be required for, or involved inovarian cancer tumorigenesis.

SEQ. ID. NO:15

The candidate protein encoded by the isolated SEQ. ID. NO:15 isassociated with a previously identified gene that encodes a hypotheticalprotein, FLJ33790, which has no known function (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 15), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:16

The STAR sequence represented by the isolated SEQ. ID. NO:16 maps to apreviously identified est, BG213598 that is from a transcribed genomiclocus contained in the Unigene cluster, Hs.334302, which encodes a yetunknown protein (see Table 2). We have demonstrated that this STAR clonesequence is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 16), which have not been previously reported. Thus, it is believedthat expression of the gene corresponding to this STAR sequence (andpolynucleotides comprising this STAR sequence) or a related gene memberas is outlined in the Unigene cluster may be required for, or involvedin ovarian cancer tumorigenesis.

SEQ. ID. NO:17

The candidate protein encoded by the isolated SEQ. ID. NO:17 isassociated with a previously identified gene that encodes a protein,V-set domain containing T cell activation inhibitor 1 (VTCN1), which hasno known function (see Table 2). We have demonstrated that expression ofthis gene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 17), which have not been previously reported. Thus, it is believedthat expression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:18

The candidate protein encoded by the isolated SEQ. ID. NO:18 isassociated with a previously identified gene that encodes a protein,kinesin family member 20A (KIF20A), which is involved in cell divisionin and membrane traffic within the Golgi apparatus (see Table 2). Wehave demonstrated that expression of this gene is markedly upregulatedin malignant ovarian cancer samples compared to ovarian LMP samples anda majority of normal human tissues (FIG. 18), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:19

The STAR sequence represented by the isolated SEQ. ID. NO:19 maps to agenomic hit, Accession #AY769439 and to a group of ests represented byAccession #AA744939. The ests are clustered into Unigene identifier,Hs.478368 representing the protein, potassium large conductancecalcium-activated channel, subfamily M, beta member 2 (KCNMB2). However,the STAR sequence does not overlap with any of the mRNA sequences listedthus far in the Hs.478368 Unigene cluster (see Table 2). We havedemonstrated that this STAR clone sequence is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 19A), which have not beenpreviously reported. In addition, performing RT-PCR using primersspecific to either the STAR clone sequence for SEQ. ID. NO. 19 or theKCNMB2 sequence represented by Accession No. NM_005832, theamplification profiles were not the same across a number of ovariansamples tested (FIG. 19B). It was obvious that KCNMB2 was expressed inessentially all ovarian samples including the normal at similar levelswhereas, PCR amplicons for SEQ. ID. NO. 19 was observed at higher levelsin the malignant ovarian tumor samples compared to the LMPs and normalovarian samples (FIG. 19B). Thus, it is believed that the expression ofthe gene corresponding to this STAR sequence (and polynucleotidesequences comprising the STAR sequence) or a related gene member may berequired for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:20

The STAR sequence represented by the isolated SEQ. ID. NO:20 maps to apreviously identified est, BU595315 belonging to a group of ests that isfrom a transcribed genomic locus contained in the Unigene cluster,Hs.603908, which encodes a yet unknown protein (see Table 2). We havedemonstrated that this STAR clone sequence is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 20), which have not beenpreviously reported. Thus, it is believed that expression of the genecorresponding to this STAR sequence (and polynucleotide sequencescomprising this STAR sequence) or a related gene member as is outlinedin the Unigene cluster may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:21

The candidate protein encoded by the isolated SEQ. ID. NO:21 is apreviously identified gene that encodes a protein, chemokine (C-X-Cmotif) ligand 10 (CXCL10), which has chemokine activity (see Table 2).We have demonstrated that expression of this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 21), which have notbeen previously reported. Thus, it is believed that expression of thegene may be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:22

The STAR sequence represented by the isolated SEQ. ID. NO:22 maps tochromosome 14, and may represent a portion of an unknown gene sequence(see Table 2). We have demonstrated that this STAR clone sequence ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 22),which have not been previously reported. Thus, it is believed thatexpression of the gene corresponding to this STAR sequence (andpolynucleotides comprising this STAR sequence) may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:23

The candidate protein encoded by the isolated SEQ. ID. NO:23 is apreviously identified gene that encodes a protein, asparagine-linkedglycosylation 8 homolog (yeast, alpha-1,3-glucosyltransferase) (ALG8),which catalyzes the addition of the second glucose residue to thelipid-linked oligosaccharide precursor for N-linked glycosylation ofproteins (see Table 2). We have demonstrated that expression of thisgene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 23), which have not been previously reported. Thus, it is believedthat expression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:24

The candidate protein encoded by the isolated SEQ. ID. NO:24 is apreviously identified gene that encodes a protein, kidney associatedantigen 1 (KAAG1), which has no known function (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 24), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:25

The candidate protein encoded by the isolated SEQ. ID. NO:25 is apreviously identified gene that encodes a protein, cyclin-dependentkinase inhibitor 2A (CDKN2A), which is involved in cell cycle control,G1/S Checkpoint (see Table 2). We have demonstrated that expression ofthis gene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 25), which have not been previously reported. Thus, it is believedthat expression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:26

The candidate protein encoded by the isolated SEQ. ID. NO:26 is apreviously identified gene that encodes a protein,microtubule-associated protein homolog (Xenopus laevis) (TPX2), which isinvolved in cell proliferation from the transition G1/S until the end ofcytokinesis (see Table 2). We have demonstrated that expression of thisgene is markedly upregulated in malignant ovarian cancer samplescompared to ovarian LMP samples and a majority of normal human tissues(FIG. 26), which have not been previously reported. Thus, it is believedthat expression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:27

The candidate protein encoded by the isolated SEQ. ID. NO:27 is apreviously identified gene that encodes a protein, ubiquitin-conjugatingenzyme E2C (UBE2C), which is required for the destruction of mitoticcyclins and for cell cycle progression (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 27), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:28

The STAR sequence represented by the isolated SEQ. ID. NO:28 maps tocDNA FLJ35538 f is, clone SPLEN2002463 of Unigene cluster, Hs.590469 andmay represent a portion of an unknown gene sequence (see Table 2). Wehave demonstrated that this STAR clone sequence is markedly upregulatedin malignant ovarian cancer samples compared to ovarian LMP samples anda majority of normal human tissues (FIG. 28), which have not beenpreviously reported. Thus, it is believed that expression of the genecorresponding to this STAR sequence (and polynucleotides comprising thisSTAR sequence) or a related gene member as is outlined in the Unigenecluster may be required for, or involved in ovarian cancertumorigenesis.

SEQ. ID. NO:29

The candidate protein encoded by the isolated SEQ. ID. NO:29 is apreviously identified gene that encodes a protein, cellular retinoicacid binding protein 2 (CRABP2), whose function has not been preciselydetermined but this isoform is important in retinoic acid-mediatedregulation of human skin growth and differentiation (see Table 2). Wehave demonstrated that expression of this gene is markedly upregulatedin malignant ovarian cancer samples compared to ovarian LMP samples anda majority of normal human tissues (FIG. 29), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:30

The candidate protein encoded by the isolated SEQ. ID. NO:30 is apreviously identified gene that encodes a protein, Histone 3, H2a(HIST3H2A), which is involved in nucleosome formation (see Table 2). Wehave demonstrated that expression of this gene is markedly upregulatedin malignant ovarian cancer samples compared to ovarian LMP samples anda majority of normal human tissues (FIG. 30), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:31

The candidate protein encoded by the isolated SEQ. ID. NO:31 is apreviously identified gene that encodes a protein, Histone 1, H4 h(HIST1H4H), which is involved in nucleosome formation (see Table 2). Wehave demonstrated that expression of this gene is markedly upregulatedin malignant ovarian cancer samples compared to ovarian LMP samples anda majority of normal human tissues (FIG. 30), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:32

The candidate protein encoded by the isolated SEQ. ID. NO:32 is apreviously identified gene that encodes a hypothetical protein, Homeobox D3 (HOXD3), which is a nuclear transcription factor involved indevelopment and differentiation (see Table 2). We have demonstrated thatexpression of this gene is markedly upregulated in malignant ovariancancer samples compared to ovarian LMP samples and a majority of normalhuman tissues (FIG. 32), which have not been previously reported. Thus,it is believed that expression of the gene may be required for ovariancancer tumorigenesis.

SEQ. ID. NO:33

The candidate protein encoded by the isolated SEQ. ID. NO:33 is apreviously identified gene that encodes a member of the immunoglobulingene family, immunoglobulin constant gamma 1 (IGHG1), which probablyplays a role in immune response and antigen binding (see Table 2). Wehave demonstrated that expression of this gene is markedly upregulatedin malignant ovarian cancer samples compared to ovarian LMP samples anda majority of normal human tissues (FIG. 33), which have not beenpreviously reported. The expression pattern of this gene is similar totwo other genes disclosed here, SEQ. ID. NO. 34 and SEQ. ID. NO. 47,which also encode immunoglobulins. This type of clustered immunoglobulinexpression in ovarian cancer has not been previously described. Thus, itis believed that expression of the gene may be required for ovariancancer tumorigenesis.

SEQ. ID. NO:34

The candidate protein encoded by the isolated SEQ. ID. NO:34 is apreviously identified gene that encodes a member of the immunoglobulingene family, immunoglobulin kappa constant (IGKC), which probably playsa role in immune response and antigen binding (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 34), which have not beenpreviously reported. The expression pattern of this gene is similar totwo other genes disclosed here, SEQ. ID. NO. 33 and SEQ. ID. NO. 47,which also encode immunoglobulins. This type of clustered immunoglobulinexpression in ovarian cancer has not been previously described. Thus, itis believed that expression of the gene may be required for ovariancancer tumorigenesis.

SEQ. ID. NO:35

The candidate protein encoded by the isolated SEQ. ID. NO:35 is a genelocated on chromosome 10 that encodes an open reading frame of unknownfunction. (see Table 2). The gene may encode a protein termedastroprincin that was found to be expressed in a critical region inDiGeorge syndrome. We have demonstrated that expression of this gene ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 35),which have not been previously reported. Thus, it is believed thatexpression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:36

The candidate protein encoded by the isolated SEQ. ID. NO:36 is apreviously identified gene that encodes a protein, histocompatibility(minor) 13 (HM13), which has no known function (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 36), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:37

The STAR sequence represented by the isolated SEQ. ID. NO:37 maps tochromosome 13, and may represent a portion of an unknown gene sequence(see Table 2). We have demonstrated that this STAR clone sequence ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 37),which have not been previously reported. Thus, it is believed thatexpression of the gene corresponding to this STAR sequence (andpolynucleotides comprising this STAR sequence) may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:38

The candidate protein encoded by the isolated SEQ. ID. NO:38 is apreviously identified gene that encodes a protein, frizzled-relatedprotein (FRZB), which is associated with symptomatic osteoarthritis andmay play a role in skeletal morphogenesis (see Table 2). We havedemonstrated that expression of this gene is markedly upregulated inmalignant ovarian cancer samples compared to ovarian LMP samples and amajority of normal human tissues (FIG. 38), which have not beenpreviously reported. Thus, it is believed that expression of the genemay be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:39

The candidate protein encoded by the isolated SEQ. ID. NO:39 is apreviously identified gene that encodes a protein, forkhead box M1(FOXM1), which is a transcription factor that regulates genes involvedin cell proliferation (see Table 2). We have demonstrated thatexpression of this gene is markedly upregulated in malignant ovariancancer samples compared to ovarian LMP samples and a majority of normalhuman tissues (FIG. 39), which have not been previously reported. Thus,it is believed that expression of the gene may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:40

The candidate protein encoded by the isolated SEQ. ID. NO:40 is a genelocated on chromosome 20 that encodes an open reading frame of unknownfunction. (see Table 2). The gene is predicted to encode a membraneprotein. We have demonstrated that expression of this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 40), which have notbeen previously reported. Thus, it is believed that expression of thegene may be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:41

The STAR sequence represented by the isolated SEQ. ID. NO:41 maps tochromosome 1, and may represent a portion of an unknown gene sequence(see Table 2). Weak homology has been found between SEQ. ID. NO. 41 andthe envelop proteins present at the surface of human endogenousretroviruses. We have demonstrated that this STAR clone sequence ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 41),which have not been previously reported. Thus, it is believed thatexpression of the gene corresponding to this STAR sequence (andpolynucleotides comprising this STAR sequence) may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:42

The candidate protein encoded by the isolated SEQ. ID. NO:42 is a genelocated on chromosome 16 that encodes an open reading frame of unknownfunction. (see Table 2). The gene is predicted to encode a membraneprotein. We have demonstrated that expression of this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 42), which have notbeen previously reported. Thus, it is believed that expression of thegene may be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:43

The candidate protein encoded by the isolated SEQ. ID. NO:43 is apreviously identified gene that encodes a protein, Rac GTPase activatingprotein 1 (RACGAP1), which is a GTPase that interacts with Rho GTPasesto control many cellular processes (see Table 2). These types ofproteins are important effector molecules for the downstream signalingof Rho GTPases. We have demonstrated that expression of this gene ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 43),which have not been previously reported. Thus, it is believed thatexpression of the gene may be required for, or involved in ovariancancer tumorigenesis.

SEQ. ID. NO:44

The candidate protein encoded by the isolated SEQ. ID. NO:44 is a genethat encodes transmembrane protein 19 (TMEM19) that has no knownfunction. (see Table 2). The gene is predicted to encode a membraneprotein. We have demonstrated that expression of this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 44), which have notbeen previously reported. Thus, it is believed that expression of thegene may be required for, or involved in ovarian cancer tumorigenesis.

SEQ. ID. NO:45

The STAR sequence represented by the isolated SEQ. ID. NO:45 maps tochromosome 4, and may represent a portion of an unknown gene sequence(see Table 2). We have demonstrated that this STAR clone sequence ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 45),which have not been previously reported. Thus, it is believed thatexpression of the gene corresponding to this STAR sequence (andpolynucleotides comprising this STAR sequence) may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:46

The STAR sequence represented by the isolated SEQ. ID. NO:46 maps tochromosome 1, and may represent a portion of an unknown gene sequence(see Table 2). We have demonstrated that this STAR clone sequence ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 46),which have not been previously reported. Thus, it is believed thatexpression of the gene corresponding to this STAR sequence (andpolynucleotides comprising this STAR sequence) may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:47

The candidate protein encoded by the isolated SEQ. ID. NO:47 is apreviously identified gene with the Unigene cluster, Hs.449585, and mayrepresent a portion immunoglobulin lambda locus (IGLV@), which probablyplays a role in immune response and antigen binding (see Table 2). Wehave demonstrated that expression of this gene is markedly upregulatedin malignant ovarian cancer samples compared to ovarian LMP samples anda majority of normal human tissues (FIG. 47), which have not beenpreviously reported. The expression pattern of this gene is similar totwo other genes disclosed here, SEQ. ID. NO. 33 and SEQ. ID. NO. 34,which also encode immunoglobulins. This type of clustered immunoglobulinexpression in ovarian cancer has not been previously described. Thus, itis believed that expression of the gene may be required for ovariancancer tumorigenesis.

SEQ. ID. NO:48

The candidate protein encoded by the isolated SEQ. ID. NO:48 is apreviously identified gene that encodes a protein, secretory carriermembrane protein 3 (SCAMP3), which functions as a cell surface carrierprotein during vesicular transport (see Table 2). We have demonstratedthat expression of this gene is markedly upregulated in malignantovarian cancer samples compared to ovarian LMP samples but it is alsoexpressed in a majority of normal human tissues (FIG. 48), which havenot been previously reported. Thus, it is believed that expression ofthe gene may be required for, or involved in ovarian cancertumorigenesis.

SEQ. ID. NO:49

The STAR sequence represented by the isolated SEQ. ID. NO:49 maps tochromosome 2, and may represent a portion of an unknown gene sequence(see Table 2). We have demonstrated that this STAR clone sequence ismarkedly upregulated in malignant ovarian cancer samples compared toovarian LMP samples and a majority of normal human tissues (FIG. 49),which have not been previously reported. Thus, it is believed thatexpression of the gene corresponding to this STAR sequence (andpolynucleotides comprising this STAR sequence) may be required for, orinvolved in ovarian cancer tumorigenesis.

SEQ. ID. NO:50

The candidate protein encoded by the isolated SEQ. ID. NO:50 is apreviously identified gene that encodes a protein, Folate receptor 1(adult) (FOLR1), with members of this gene family having a high affinityfor folic acid and for several reduced folic acid derivatives, andmediate delivery of 5-methyltetrahydrofolate to the interior of cells(see Table 2). We have demonstrated that this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 50). The potentialrole of FOLR1 in ovarian cancer therapeutics has been previouslydocumented (Leamon and Low, 2001 and Jhaveri et al., 2006, U.S. Pat. No.7,030,236). By way of example of the FOLR1 gene target, similar genesdescribed herein with upregulation in malignant ovarian tumors andlimited or no expression in a majority of normal tissues may also serveas potential therapeutic targets for ovarian cancer.

SEQ. ID. NO:169

The candidate protein encoded by the isolated SEQ. ID. NO:169 is apreviously identified gene that encodes a protein, ceruloplasmin (CP),that binds most of the copper in plasma and is involved in theperoxidation of Fe(II)transferrin. The deficiency of thismetalloprotein, termed aceruloplasminemia, leads to iron accumulationand tissue damage, and is associated diabetes and neurologic diseases(see Table 2). We have demonstrated that this gene is markedlyupregulated in malignant ovarian cancer samples compared to ovarian LMPsamples and a majority of normal human tissues (FIG. 56) which have notbeen previously reported. Thus, it is believed that expression of thegene corresponding to this STAR sequence (and polynucleotides comprisingthis STAR sequence) may be required for, or involved in ovarian cancertumorigenesis.

H—RNA Interference Studies

RNA interference is a recently discovered gene regulation mechanism thatinvolves the sequence-specific decrease in a gene's expression bytargeting the mRNA for degradation and although originally described inplants, it has been discovered across many animal kingdoms fromprotozoans and invertebrates to higher eukaryotes (reviewed in Agrawalet al., 2003). In physiological settings, the mechanism of RNAinterference is triggered by the presence of double-stranded RNAmolecules that are cleaved by an RNAse III-like protein active in cells,called Dicer, which releases the 21-23 bp siRNAs. The siRNA, in ahomology-driven manner, complexes into a RNA-protein amalgamation termedRISC (RNA-induced silencing complex) in the presence of mRNA to causedegradation resulting in attenuation of that mRNA's expression (Agrawalet al., 2003).

Current approaches to studying the function of genes, such as geneknockout mice and dominant negatives, are often inefficient, andgenerally expensive, and time-consuming. RNA interference is proving tobe a method of choice for the analysis of a large number of genes in aquick and relatively inexpensive manner. Although transfection ofsynthetic siRNAs is an efficient method, the effects are often transientat best (Hannon G. J., 2002). Delivery of plasmids expressing shorthairpin RNAs by stable transfection has been successful in allowing forthe analysis of RNA interference in longer-term studies (Brummelkamp etal., 2002; Elbashir et al., 2001).

I—Determination of Knockdown Effects on the Proliferation of OvarianCancer Cell Lines

In order to determine which ovarian cancer-specific genes participate inthe proliferation of ovarian cancer cells, an assay was developed usingstably transfected cell lines that contain attenuated (i.e., knockeddown) levels of the specific gene being investigated. Two human ovariancancer cell lines derived from chemotherapy-naïve patients were utilizedthat have been previously characterized in terms of their morphology,tumorigenicity, and global expression profiles. In addition, theseanalyses revealed that these cell lines were excellent models for invivo behavior of ovarian tumors in humans (Provencher et al., 2000 andSamouelian et al., 2004). These cell lines are designated TOV-21G andTOV-112D.

The design and subcloning of individual shRNA expression cassettes andthe procedure utilized for the characterisation of each nucleotidesequence is described below. Selection of polynucleotides were chosenbased on their upregulation in ovarian tumors and the selective natureof their expression in these tumors compared to other tissues asdescribed above. The design of shRNA sequences was performed usingweb-based software that is freely available to those skilled in the art(Qiagen for example). These chosen sequences, usually 19-mers, wereincluded in two complementary oligonucleotides that form the templatefor the shRNAs, i.e. the 19-nt sense sequence, a 9-nt linker region(loop), the 19-nt antisense sequence followed by a 5-6 poly-T tract fortermination of the RNA polymerase III. Appropriate restriction siteswere inserted at the ends of these oligonucleotides to facilitate properpositioning of the inserts so that the transcriptional start point is ata precise location downstream of the hU6 promoter. The plasmid utilizedin all RNA interference studies, pSilencer 2.0 (SEQ. ID. NO. 101), waspurchase from a commercial supplier (Ambion, Austin, Tex.). For eachsequence selected, at least two different shRNA expression vectors wereconstructed to increase the chance of observing RNA interference.

TOV-21G or TOV-112D cells were seeded in 6-well plates in OSE(Samouelian et al., 2004) containing 10% fetal bovine serum at a densityof 600 000 cells/well, allowed to plate overnight and transfected with 1μg of pSil-shRNA plasmid (FIG. 53, sh-1 and sh-2) using the Fugene 6reagent (Roche, Laval, QC). After 16 h of incubation, fresh medium wasadded containing 2 μg/ml puromycin (Sigma, St. Louis, Mo.) to select forstable transfectants. Control cells were transfected with a control pSil(sh-scr (SEQ. ID. NO. 102) that contains a scrambled shRNA sequence thatdisplays homology to no known human gene. After approximately 4-5 days,pools and/or individual clones of cells were isolated and expanded forfurther analyses. The effectiveness of attenuation was verified in allshRNA cells lines. Total RNA was prepared by standard methods usingTrizol™ reagent from cells grown in 6-well plates and expression of thetarget gene was determined by RT-PCR using gene-specific primers. Firststrand cDNA was generated using Thermoscript (Invitrogen, Burlington,ON) and semi-quantitative PCR was performed by standard methods (Qiagen,Mississauga, ON). 100% expression levels for a given gene was assignedto those found in the cell lines transfected with the control pSilplasmid (sh-scr). FIG. 52 shows representative results from theattenuation of two candidate genes, SEQ. ID. NO. 1 and SEQ. ID. NO. 3.When RT-PCR was performed using total RNA from the control cell lines(FIG. 52, pSil-scr), a single band of expected size was observed. Whenthe total RNA from the cell line containing shRNAs to SEQ. ID. NO. 1(0094) (sh-1: SEQ. ID. NO. 103 and sh-2: SEQ. ID. NO. 104) or SEQ. ID.NO. 3 (0671) (sh-1: SEQ. ID. NO. 107 and sh-2: SEQ. ID. NO. 108) wasamplified under identical conditions, significant reduction in thelevels of expression of these genes were observed. These resultsindicate that the shRNAs that were expressed in the TOV-21G stabletransfectants were successful in attenuating the expression of theirtarget genes. As a control for equal quantities of RNA in all reactions,the expression of glyceraldehyde-3-phosphate dehydrogenase (FIG. 52,GAPDH) was monitored and found to be expressed at equal levels in allsamples used.

The proliferative ability of each shRNA-expressing cell line wasdetermined and compared to cells expressing the scrambled shRNA(control). Cell number was determined spectrophotometrically by MTTassay at 570 nm (Mosmann, 1983). After selection of stably shRNAexpressing pools and expansion of the lines, 5 000 cells/well of eachcell lines was plated in 48-well plates in triplicate and incubated for4 days under standard growth conditions. Representative data from 2experiments ±SEM is displayed and experiments were typically repeated atleast three times to confirm the results observed. FIG. 53 showsrepresentative results that were obtained when the proliferation assaywas applied to stable TOV-21G cells lines. The cell number after 4 daysin the control cell line expressing the scrambled shRNA (FIG. 53, shscr) was arbitrarily set to 100%. TOV-21G cell lines containing shRNAagainst SEQ. ID. NO. 1 (sh-1: SEQ. ID. NO. 103 and sh-2: SEQ. ID. NO.104), SEQ. ID. NO. 3 (sh-1: SEQ. ID. NO. 107 and sh-2: SEQ. ID. NO. 108)and SEQ. ID. NO. 8 (0065) (sh-1: SEQ. ID. NO. 117 and sh-2: SEQ. ID. NO.118) exhibited less than 50% proliferation for at least one shRNAcompared to the control cell line (FIG. 53, sh-1 and sh-2 for each). Theproliferation of TOV-21G cell lines containing shRNA against SEQ. ID.NO. 2 (0478) (sh-1: SEQ. ID. NO. 105 and sh-2: SEQ. ID. NO. 106) andSEQ. ID. NO. 7 (1096) (sh-1: SEQ. ID. NO. 115 and sh-2: SEQ. ID. NO.116) was not affected to the same extent but significant inhibition ofgrowth was still observed nevertheless. These results indicate thatattenuation of these genes causes retardation in the growth of thisovarian cancer cell line. Several of these shRNA expression vectors werealso transfected into the TOV-112D cell line and similar results wereobtained (data not shown). This suggested that these genes are importantfor proliferation of ovarian cancer cells.

The gene encoding the folate receptor 1, SEQ. ID. NO. 50 (0967A) (FIG.53, 0967A), which has been documented as being an important marker forovarian cancer (Leamon and Low, 2001), was also attenuated in TOV-21Gcells, and marked growth inhibition was observed in the presence of theshRNAs (sh-1: SEQ. ID. NO. 151 and sh-2: SEQ. ID. NO. 152). This givescredibility to the approach used to validate the genes presented in thispatent and substantiated their functional importance in theproliferation of ovarian cancer cells.

Table 1 below lists all of the genes tested and the average growthinhibition (n=3-4) that was observed in TOV-21G cells. Differences ofless than 20% (see Table 1, <20) compared to the control cell linesrepresent cells where statistically significant reduction inproliferation was measured within a range of 5-20%.

TABLE 1 List of genes tested in cell proliferation assay and resultsAverage Growth Alethia's inhibition in Gene SEQ. ID. Gene TOV-21G cellsNO. Code shRNA SEQ. ID. NO. (%) (n = 3-4) Control SEQ. ID. NO. 102 0SEQ. ID. NO. 1 0094 SEQ. ID. NOs. 103 47.9 and 104 SEQ. ID. NO. 2 0478SEQ. ID. NOs. 105 41.7 and 106 SEQ. ID. NO. 3 0671 SEQ. ID. NOs. 10765.7 and 108 SEQ. ID. NO. 4 0851 SEQ. ID. NOs. 109 21.5 and 110 SEQ. ID.NO. 5 0713 SEQ. ID. NOs. 111 42.3 and 112 SEQ. ID. NO. 6 1064 SEQ. ID.NOs. 113 28.9 and 114 SEQ. ID. NO. 7 1096 SEQ. ID. NOs. 115 25.8 and 116SEQ. ID. NO. 8 0065 SEQ. ID. NOs. 117 32.5 and 118 SEQ. ID. NO. 9 1313SEQ. ID. NOs. 119 50.5 and 120 SEQ. ID. NO. 0059 SEQ. ID. NOs. 121 52.410 and 122 SEQ. ID. NO. 0239 SEQ. ID. NOs. 123 22.8 11 and 124 SEQ. ID.NO. 0291 SEQ. ID. NOs. 125 <20 12 and 126 SEQ. ID. NO. 0972 SEQ. ID.NOs. 127 <20 13 and 128 SEQ. ID. NO. 0875 SEQ. ID. NOs. 129 <20 14 and130 SEQ. ID. NO. 0420 SEQ. ID. NOs. 131 <20 15 and 132 SEQ. ID. NO. 0125SEQ. ID. NOs. 133 <20 16 and 134 SEQ. ID. NO. 0531 SEQ. ID. NOs. 135 017 and 136 SEQ. ID. NO.   0967B SEQ. ID. NOs. 137 0 18 and 138 SEQ. ID.NO. 0889 SEQ. ID. NOs. 139 <20 19 and 140 SEQ. ID. NO. 0313 SEQ. ID.NOs. 141 <20 20 and 142 SEQ. ID. NO. 1134 SEQ. ID. NOs. 143 <20 21 and144 SEQ. ID. NO. 0488 SEQ. ID. NOs. 145 0 22 and 146 SEQ. ID. NO. 0216SEQ. ID. NOs. 147 <20 23 and 148 SEQ. ID. NO. 0447 SEQ. ID. NOs. 149 024 and 150 SEQ. ID. NO.   0967A SEQ. ID. NOs. 151 47.4 50 and 152

J—a Method for Determining the Requirement for Specific Genes in theSurvival of Ovarian Cancer Cells

As a means of complementing the growth inhibition data that wasgenerated with the stable TOV-21G cell lines, a colony survival assaywas used to determine the requirement of the selected genes in thesurvival of the cancer cells. The ‘colony formation assay’ or‘clonogenic assay’ is a classical test to evaluate cell growth aftertreatment. The assay is widespread in oncological research areas whereit is used to test the proliferating power of cancer cell lines afterradiation and/or treatment with anticancer agents. It was expected thatthe results obtained when analyzing the genes that were functionallyimportant in ovarian cancer would correlate between the growthinhibition study and the colony survival assay.

TOV-21G cells were seeded in 12-well plates at a density of 50 000cells/well and transfected 24 h later with 1 μg of pSil-shRNA vector,the same plasmids used in the previous assay. The next day, fresh mediumwas applied containing 2 μg/ml puromycin and the selection of the cellswas carried out for 3 days. The cells were washed and fresh mediumwithout puromycin was added and growth continued for another 5 days. Tovisualize the remaining colonies, the cells were washed in PBS and fixedand stained simultaneously in 1% crystal violet/10% ethanol in PBS for15 minutes at room temperature. Following extensive washing in PBS, thedried plates were scanned for photographic analysis.

As shown in FIG. 37 and as exemplified by SEQ. ID. NO. 1 (0094), SEQ.ID. NO. 3 (0671), and SEQ. ID. NO. 9 (1313), the amount ofTOV-21G-derived colonies that survived correlated with the growthinhibition data. For example, the growth inhibition in the proliferationassay (FIG. 53) and cell death in the colony assay (FIG. 54) was greaterin TOV-21G cells containing shRNA-2 compared to shRNA-1 for SEQ. ID. NO.1 (0094) (0094-sh2 stronger than 0094-sh1) and SEQ. ID. NO. 3 (0671)(0671-sh2 stronger than 0671-sh1) whereas, for SEQ. ID. NO. 9 (1313),the 1313-sh1 was stronger than 1313-sh2. Similar convergence wasobserved with several other genes that were analyzed using these twoassays (data not shown). Therefore, these results implied that aphenotypic manifestation in both assays was indicative of importantgenes that are functionally required in ovarian cancer cells and suggestthat inhibition of the proteins they encode could be serve as importanttargets to develop new anticancer drugs.

K—A Method for Broadening the Scope of Intervention to Other OncologyIndications

One skilled in the art will recognize that the sequences described inthis invention have utilities in not only ovarian cancer, but theseapplications can also be expanded to other oncology indications wherethe genes are expressed. To address this, a PCR-based method was adaptedto determine the expression pattern of all sequences described above incancer cell lines isolated from nine types of cancer. The cancer typesrepresented by the cell lines are leukemia, central nervous system,breast, colon, lung, melanoma, ovarian, prostate, and renal cancer (seeTable C). These RNA samples were obtained from the DevelopmentalTherapeutics Program at the NCI/NIH. Using the same RAMP RNA samplesthat amplified from the total RNA samples obtained from the NCI, 500 μgof RNA was converted to single-stranded cDNA with Thermoscript RT(Invitrogen, Burlington, ON) as described by the manufacturer. The cDNAreaction was diluted so that 1/200 of the reaction was used for each PCRexperiment. After trial PCR reactions with gene-specific primersdesigned against each SEQ. ID NOs. to be tested, the linear range of thereaction was determined and applied to all samples, PCR was conducted in96-well plates using Hot-Start Taq Polymerase from Qiagen (Mississauga,ON) in a DNA Engine Tetrad from MJ Research. Half of the reactionmixture was loaded on a 1.2% agarose/ethidium bromide gel and theamplicons visualized with UV light. To verify that equal quantities ofRNA was used in each reaction, the level of RNA was monitored with GAPDHexpression.

TABLE C List of cancer cell lines from the NCI-60 panel Cell line Cancertype K-562 leukemia MOLT-4 leukemia CCRF-CEM leukemia RPMI-8226 leukemiaHL-60(TB) leukemia SR leukemia SF-268 CNS SF-295 CNS SF-539 CNS SNB-19CNS SNB-75 CNS U251 CNS BT-549 breast HS 578T breast MCF7 breastNCI/ADR-RES breast MDA-MB-231 breast MDA-MB-435 breast T-47D breast COLO205 colon HCC-2998 colon HCT-116 colon HCT-15 colon HT29 colon KM12colon SW-620 colon A549/ATCC non-small cell lung EKVX non-small celllung HOP-62 non-small cell lung HOP-92 non-small cell lung NCI-H322Mnon-small cell lung NCI-H226 non-small cell lung NCI-H23 non-small celllung NCI-H460 non-small cell lung NCI-H522 non-small cell lung LOX IMVImelanoma M14 melanoma MALME-3M melanoma SK-MEL-2 melanoma SK-MEL-28melanoma SK-MEL-5 melanoma UACC-257 melanoma UACC-62 melanoma IGROV-1ovarian OVCAR-3 ovarian OVCAR-4 ovarian OVCAR-5 ovarian OVCAR-8 ovarianSK-OV-3 ovarian DU-145 prostate PC-3 prostate 786-O renal A498 renalACHN renal CAKI-1 renal RXF-393 renal SN-12C renal TK-10 renal UO-31renal

One of skill in the art will readily recognize that orthologues for allmammals maybe identified and verified using well-established techniquesin the art, and that this disclosure is in no way limited to one mammal.The term “mammal(s)” for purposes of this disclosure refers to anyanimal classified as a mammal, including humans, domestic and farmanimals, and zoo, sports, or pet animals, such as dogs, cats, cattle,horses, sheep, pigs, goats, rabbits, etc. Preferably, the mammal ishuman.

The sequences in the experiments discussed above are representative ofthe NSEQ being claimed and in no way limit the scope of the invention.The disclosure of the roles of the NSEQs in proliferation of ovariancancer cells satisfies a need in the art to better understand ovariancancer disease, providing new compositions that are useful for thediagnosis, prognosis, treatment, prevention and evaluation of therapiesfor ovarian cancer and other cancers where said genes are expressed aswell.

The art of genetic manipulation, molecular biology and pharmaceuticaltarget development have advanced considerably in the last two decades.It will be readily apparent to those skilled in the art that newlyidentified functions for genetic sequences and corresponding proteinsequences allows those sequences, variants and derivatives to be useddirectly or indirectly in real world applications for the development ofresearch tools, diagnostic tools, therapies and treatments for disordersor disease states in which the genetic sequences have been implicated.

Although the present invention has been described herein above by way ofpreferred embodiments thereof, it maybe modified, without departing fromthe spirit and nature of the subject invention as defined in theappended claims.

TABLE 2 Differentially expressed sequences found in malignant ovariancancer. NCBI ORF Unigene Nucleotide #/Gene Positions/ NucleotideSymbol/Gene Accession Polypeptide Sequence No. ID Number sequence No.Function SEQ ID NO. 1 STAR clone BX094904 Unknown Transcribed locus butpossibly NM_021955 149-373 for guanine nucleotide belonging to forHs.555871 binding protein (G cluster Hs.555871 encoding SEQ protein),gamma Hs.555871 ID NO.: 51 transducing activity polypeptide 1 SEQ ID NO.2 Hs.389724/ NM_006820 242-1483 interferon-induced IFI44L/ encoding SEQprotein 44-like; 10964 ID NO.: 52 function unknown SEQ ID NO. 3Hs.83465/ NM_024501 224-1210 homeobox D1; HOXD1/ encoding SEQsequence-specific 3231 ID NO.: 53 transcription factor that is involvedin differentiation and limb development SEQ ID NO. 4 Hs.59761/NM_001017920 45-368 hypothetical protein LOC92196/ encoding SEQLOC92196; 92196 ID NO.: 54 function unknown SEQ ID NO. 5 Hs.20315/NM_001001887 93-1529 interferon-induced IFIT1/ encoding SEQ protein with3434 ID NO.: 55 tetratricopeptide repeats 1; function unknown SEQ ID NO.6 Hs.584238/ NM_000170 151-3213 glycine GLDC/ encoding SEQ dehydrogenase2731 ID NO.: 56 (decarboxylating; glycine decarboxylase, glycinecleavage system protein P); mitochondrial glycine cleavage systemcatalyzes the degradation of glycine SEQ ID NO. 7 Hs.302028/ NM_0223579-1550 dipeptidase 3; DPEP3/ encoding SEQ proteolysis and 64180 ID NO.:57 peptidolysis SEQ ID NO. 8 Hs.418367/ NM_006681 106 . . . 630neuromedin U NMU/ encoding SEQ (NMU); neuropeptide 10874 ID NO.: 58signaling pathway, regulation of smooth muscle contraction SEQ ID NO. 9Hs.473163/ NM_001719 123-1418 bone morphogenetic BMP7/ encoding SEQprotein 7; cell growth 655 ID NO.: 59 and/or maintenance, growth,skeletal development, cytokine activity, growth factor activity SEQ IDNO. 10 Hs.84113/ NM_005192 62-700 cyclin-dependent CDKN3/ encoding SEQkinase inhibitor 3; a 1033 ID NO.: 60 cyclin-dependent kinase inhibitor,as well as, dephosphorylate CDK2 kinase which prevent the activation ofCDK2 kinase SEQ ID NO. 11 Hs.374378/ NM_001826 10-249 CDC28 proteinkinase CKS1B/ encoding SEQ regulatory subunit 1B; 1163 ID NO.: 61 cellcycle, cytokinesis, cyclin-dependent protein kinase activity SEQ ID NO.12 Hs.30743/ NM_006115 250-1779 preferentially PRAME/ encoding SEQexpressed antigen in 23532 ID NO.: 62 melanoma; function unknown SEQ IDNO. 13 Hs.458485/ NM_005101 76-573 ISG15 ubiquitin-like ISG15/ encodingSEQ modifier; 9636 ID NO.: 63 protein binding SEQ ID NO. 14 STAR cloneAI922121.1 Novel genomic hit SEQ ID NO. 15 Hs.292451/ NM_001039548220-1311 hypothetical protein FLJ33790/ encoding SEQ LOC283212; 283212ID NO.: 64 function unknown SEQ ID NO. 16 Hs.334302 BG213598 Transcribedlocus; function unknown SEQ ID NO. 17 Hs.546434/ NM_024626 71-919 V-setdomain VTCN1/ encoding SEQ containing T cell 79679 ID NO.: 65 activationinhibitor 1; function unknown SEQ ID NO. 18 Hs.73625/ NM_005733 28 . . .2700 kinesin family KIF20A/ encoding SEQ member 20A; 10112 ID NO.: 66kinesin family, interacts with guanosine triphosphate (GTP)- bound formsof RAB6A and RAB6B SEQ ID NO. 19 STAR clone AC117457 300-1007 novelgenomic hit but a possibly NM_005832 encoding SEQ potassium large of itbelonging for ID NO.: 67 conductance calcium- to cluster Hs.478368activated channel, Hs.478368 subfamily M, beta according to member 2 forNCBI Hs.478368 SEQ ID NO. 20 Hs.603908 BU595315 Transcribed locus;function unknown SEQ ID NO. 21 Hs.632586/ NM_001565 67-363 chemokine(C-X-C CXCL10/ encoding SEQ motif) ligand 10; 3627 ID NO.: 68 chemokineSEQ ID NO. 22 STAR clone AL583809 Novel genomic hit SEQ ID NO. 23Hs.503368/ NM_001007027 66-1469 asparagine-linked ALG8/ encoding SEQglycosylation 8 79053 ID NO.: 69 homolog (S. cerevisiae, alpha-1,3-glucosyltransferase); catalyzes the addition of the second glucoseresidue to the lipid-linked oligosaccharide precursor for N-linkedglycosylation of proteins SEQ ID NO. 24 Hs.591801/ NM_181337 738-992kidney associated KAAG1 encoding SEQ antigen 1; fumction ID NO.: 70unknown SEQ ID NO. 25 Hs.512599/ NM_000077 213-683 cyclin-dependentCDKN2A/ encoding SEQ kinase inhibitor 2A; 1029 ID NO.: 71 cell cycle G1control SEQ ID NO. 26 Hs.244580/ NM_012112 699-2942 TPX2, microtubule-TPX2/ encoding SEQ associated, homolog 22974 ID NO.: 72 (Xenopuslaevis); involve in cell proliferation SEQ ID NO. 27 Hs.93002/ NM_00701981-620 ubiquitin-conjugating UBE2C/ encoding SEQ enzyme E2C; 11065 IDNO.: 73 required for the destruction of mitotic cyclins and for cellcycle progression SEQ ID NO. 28 Hs.590469 AK092857 cDNA FLJ35538 fis,clone SPLEN2002463; function unknown SEQ ID NO. 29 Hs.405662/ NM_001878138-554 cellular retinoic acid CRABP2/ encoding SEQ binding protein 2;1382 ID NO.: 74 function unknown but may be involved in human skingrowth and differentiation SEQ ID NO. 30 Hs.26331/ NM_033445 43-435histone 3, H2a; HIST3H2A/ encoding SEQ nucleosome formation 92815 IDNO.: 75 SEQ ID NO. 31 Hs.591790/ NM_003543 1-312 histone 1, H4h;HIST1H4H/ encoding SEQ nucleosome formation 8365 ID NO.: 76 SEQ ID NO.32 Hs.93574/ NM_006898 177-1475 homeobox D3; may HOXD3/ encoding SEQplay a role in the 3232 ID NO.: 77 regulation of cell adhesion processesSEQ ID NO. 33 Hs.525641/ BC092518 61-1470 Immunoglobulin IGHG1/ encodingSEQ heavy constant 3500 ID NO.: 78 gamma 1; may play a role in immuneresponse and antigen binding SEQ ID NO. 34 Hs.592988/ BC073793 10-717Immunoglobulin IGKC/ encoding SEQ kappa constant; may 3514 ID NO.: 79play a role in immune response and antigen binding SEQ ID NO. 35Hs.66762 AY683003 55-2727 Chromosome 10 ORF encoding SEQ 38; unknownfunction ID NO.: 80 SEQ ID NO. 36 Hs.373741/ NM_178580 115-1299Histocompatibility SPP/ encoding SEQ (minor) 13; unknown 81502 ID NO.:81 function SEQ ID NO. 37 STAR clone AL157931 Novel genomic hit SEQ IDNO. 38 Hs.128453/ NM_001463 219-1196 Frizzled-related FRZB/ encoding SEQprotein; Wnt receptor 2487 ID NO.: 82 signaling pathway, development,skeletal, transmembrane receptor activity SEQ ID NO. 39 Hs.239/NM_202003 266-2512 Forkhead box M1; FOXM1/ encoding SEQ transcriptional2305 ID NO.: 83 regulation SEQ ID NO. 40 Hs.46627 NM_152864 89-715Chromosome 20 ORF encoding SEQ 58; unknown function ID NO.: 84 SEQ IDNO. 41 STAR clone AK092936 Novel genomic hit SEQ ID NO. 42 Gene IDBC009078 552-746 Chromosome 16 ORF 404550 encoding SEQ 74; unknownfunction ID NO.: 85 SEQ ID NO. 43 Hs.645513/ NM_013277 225-2123 RacGTPase RACGAP1/ encoding SEQ activating protein 1; 29127 ID NO.: 86electron transport, intracellular signaling cascade; iron ion bindingSEQ ID NO. 44 Hs.645522/ NM_018279 584-1594 Transmembrane TMEM19/encoding SEQ protein 19; unknown 55266 ID NO.: 87 function SEQ ID NO. 45STAR clone AC109350 Novel genomic hit SEQ ID NO. 46 STAR clone AC104837Novel genomic hit SEQ ID NO. 47 STAR clone AC002060 Immunoglobulinlambda variable group @; may play a role in antigen binding SEQ ID NO.48 Hs.200600/ NM_005698 254-1297 Secretory carrier SCAMP3/ encoding SEQmembrane protein 3; 10067 ID NO.: 88 post-Golgi transport, proteintransport SEQ ID NO. 49 STAR clone AC068288 SEQ ID NO. 50 Hs.73769/NM_000802 26-799 folate receptor 1 FOLR1/ encoding SEQ (adult); 2348 IDNO.: 89 mediate delivery of 5- methyltetrahydrofolate to the interior ofcells SEQ ID NO. 169 Hs.558314/ NM_000096 251-3448 Ceruloplasmin; CP/encoding SEQ secreted protein; 1356 ID NO.: 170 copper ion binding ortransport

TABLE 3 List of additional sequences identification of plasmids,oligonucleotides and shRNA oligonucleotides Sequence Identification nameDescription SEQ. ID. NO. 90 OGS 364 Oligo dT₁₁ + Not 1 + biotin SEQ. ID.NO. 91 OGS 594 Oligonucleotide promoter tag 1 SEQ. ID. NO. 92 OGS 595Oligonucleotide promoter tag 1 SEQ. ID. NO. 93 OGS 458 Oligonucleotidepromoter tag 2 SEQ. ID. NO. 94 OGS 459 Oligonucleotide promoter tag 2SEQ. ID. NO. 95 OGS 494 Primer for second-strand synthesis from tag 1SEQ. ID. NO. 96 OGS 302 Primer for second-strand synthesis from tag 2SEQ. ID. NO. 97 OGS 621 Oligonucleotide promoter SEQ. ID. NO. 98 OGS 622Oligonucleotide promoter SEQ. ID. NO. 99 pCATRMAN Vector for STAR SEQ.ID. NO. 100 p20 Vector for STAR SEQ. ID. NO: 101 pSilencer2.0 vectorVector for shRNA SEQ. ID. NO: 102 sh-scr Control shRNA (Ambion) SEQ. ID.NO: 103 sh-1 0094 shRNA sequence for SEQ. ID. NO. 1 SEQ. ID. NO: 104sh-2 0094 shRNA sequence for SEQ. ID. NO. 1 SEQ. ID. NO: 105 sh-1 0478shRNA sequence for SEQ. ID. NO. 2 SEQ. ID. NO: 106 sh-2 0478 shRNAsequence for SEQ ID NO. 2 SEQ. ID. NO: 107 sh-1 0671 shRNA sequence forSEQ. ID. NO. 3 SEQ. ID. NO: 108 sh-2 0671 shRNA sequence for SEQ. ID.NO. 3 SEQ. ID. NO: 109 sh-1 0851 shRNA sequence for SEQ. ID. NO. 4 SEQ.ID. NO: 110 sh-2 0851 shRNA sequence for SEQ ID NO. 4 SEQ. ID. NO: 111sh-1 0713 shRNA sequence for SEQ. ID. NO. 5 SEQ. ID. NO: 112 sh-2 0713shRNA sequence for SEQ. ID. NO. 5 SEQ. ID. NO: 113 sh-1 1064 shRNAsequence for SEQ. ID. NO. 5 SEQ. ID. NO: 114 sh-2 1064 shRNA sequencefor SEQ ID NO. 6 SEQ. ID. NO: 115 sh-1 1096 shRNA sequence for SEQ. ID.NO. 7 SEQ. ID. NO: 116 sh-2 1096 shRNA sequence for SEQ. ID. NO. 7 SEQ.ID. NO: 117 sh-1 0065 shRNA sequence for SEQ. ID. NO. 8 SEQ. ID. NO: 118sh-2 0065 shRNA sequence for SEQ ID NO. 8 SEQ. ID. NO: 119 sh-1 1313shRNA sequence for SEQ. ID. NO. 9 SEQ. ID. NO: 120 sh-2 1313 shRNAsequence for SEQ ID NO. 9 SEQ. ID. NO: 121 sh-1 0059 shRNA sequence forSEQ. ID. NO. 10 SEQ. ID. NO: 122 sh-2 0059 shRNA sequence for SEQ ID NO.10 SEQ. ID. NO: 123 sh-1 0239 shRNA sequence for SEQ. ID. NO. 11 SEQ.ID. NO: 124 sh-2 0239 shRNA sequence for SEQ ID NO. 11 SEQ. ID. NO: 125sh-1 0291 shRNA sequence for SEQ. ID. NO. 12 SEQ. ID. NO: 126 sh-2 0291shRNA sequence for SEQ ID NO. 12 SEQ. ID. NO: 127 sh-1 0972 shRNAsequence for SEQ. ID. NO. 13 SEQ. ID. NO: 128 sh-2 0972 shRNA sequencefor SEQ ID NO. 13 SEQ. ID. NO: 129 sh-1 0875 shRNA sequence for SEQ. ID.NO. 14 SEQ. ID. NO: 130 sh-2 0875 shRNA sequence for SEQ ID NO. 14 SEQ.ID. NO: 131 sh-1 0420 shRNA sequence for SEQ. ID. NO. 15 SEQ. ID. NO:132 sh-2 0420 shRNA sequence for SEQ ID NO. 15 SEQ. ID. NO: 133 sh-10125 shRNA sequence for SEQ. ID. NO. 16 SEQ. ID. NO: 134 sh-2 0125 shRNAsequence for SEQ ID NO. 16 SEQ. ID. NO: 135 sh-1 0531 shRNA sequence forSEQ. ID. NO. 17 SEQ. ID. NO: 136 sh-2 0531 shRNA sequence for SEQ ID NO.17 SEQ. ID. NO: 137 sh-1 0967B shRNA sequence for SEQ. ID. NO. 18 SEQ.ID. NO: 138 sh-2 0967B shRNA sequence for SEQ ID NO. 18 SEQ. ID. NO: 139sh-1 0889 shRNA sequence for SEQ. ID. NO. 19 SEQ. ID. NO: 140 sh-2 0889shRNA sequence for SEQ ID NO. 19 SEQ. ID. NO: 141 sh-1 0313 shRNAsequence for SEQ. ID. NO. 20 SEQ. ID. NO: 142 sh-2 0313 shRNA sequencefor SEQ ID NO. 20 SEQ. ID. NO: 143 sh-1 1134 shRNA sequence for SEQ. ID.NO. 21 SEQ. ID. NO: 144 sh-2 1134 shRNA sequence for SEQ ID NO. 21 SEQ.ID. NO: 145 sh-1 0488 shRNA sequence for SEQ. ID. NO. 22 SEQ. ID. NO:146 sh-2 0488 shRNA sequence for SEQ ID NO. 22 SEQ. ID. NO: 147 sh-10216 shRNA sequence for SEQ. ID. NO. 23 SEQ. ID. NO: 148 sh-2 0216 shRNAsequence for SEQ ID NO. 23 SEQ. ID. NO: 149 sh-1 0447 shRNA sequence forSEQ. ID. NO. 24 SEQ. ID. NO: 150 sh-2 0447 shRNA sequence for SEQ ID NO.24 SEQ. ID. NO: 151 sh-1 0967 shRNA sequence for SEQ. ID. NO. 50 SEQ.ID. NO: 152 sh-2 0967 shRNA sequence for SEQ ID NO. 50 SEQ. ID. NO: 153OGS 1077 Forward primer for SEQ ID NO. 32 SEQ. ID. NO: 154 OGS 1078Reverse primer for SEQ ID NO. 32 SEQ. ID. NO: 155 OGS 1141 Forwardprimer for SEQ ID NO. 35 SEQ. ID. NO: 156 OGS 1142 Reverse primer forSEQ ID NO. 35 SEQ. ID. NO: 157 OGS 1202 Forward primer for SEQ ID NO. 38SEQ. ID. NO: 158 OGS 1203 Reverse primer for SEQ ID NO. 38 SEQ. ID. NO:159 OGS 1212 Forward primer for SEQ ID NO. 41 SEQ. ID. NO: 160 OGS 1213Reverse primer for SEQ ID NO. 41 SEQ. ID. NO: 161 OGS 1171 Forwardprimer for SEQ ID NO. 44 SEQ. ID. NO: 162 OGS 1172 Reverse primer forSEQ ID NO. 44 SEQ. ID. NO: 163 OGS 1175 Forward primer for SEQ ID NO. 45SEQ. ID. NO: 164 OGS 1176 Reverse primer for SEQ ID NO. 45 SEQ. ID. NO:165 OGS 1282 Forward primer for SEQ ID NO. 48 SEQ. ID. NO: 166 OGS 1283Reverse primer for SEQ ID NO. 48 SEQ. ID. NO: 167 OGS 315 Forward primerfor human GAPDH SEQ. ID. NO: 168 OGS 316 Reverse primer for human GAPDHSEQ. ID NO. 171 OGS 1136 Forward primer for SEQ ID NO. 1 SEQ. ID NO. 172OGS 1044 Reverse primer for SEQ ID NO. 1 SEQ. ID NO. 173 OGS 1250Forward primer for SEQ ID NO. 2 SEQ. ID NO. 174 OGS 1251 Reverse primerfor SEQ ID NO. 2 SEQ. ID NO. 175 OGS 1049 Forward primer for SEQ ID NO.3 SEQ. ID NO. 176 OGS 1050 Reverse primer for SEQ ID NO. 3 SEQ. ID NO.177 OGS 1051 Forward primer for SEQ ID NO. 4 SEQ. ID NO. 178 OGS 1052Reverse primer for SEQ ID NO. 4 SEQ. ID NO. 179 OGS 1252 Forward primerfor SEQ ID NO. 5 SEQ. ID NO. 180 OGS 1253 Reverse primer for SEQ ID NO.5 SEQ. ID NO. 181 OGS 1083 Forward primer for SEQ ID NO. 6 SEQ. ID NO.182 OGS 1084 Reverse primer for SEQ ID NO. 6 SEQ. ID NO. 183 OGS 1053Forward primer for SEQ ID NO. 7 SEQ. ID NO. 184 OGS 1054 Reverse primerfor SEQ ID NO. 7 SEQ. ID NO. 185 OGS 1037 Forward primer for SEQ ID NO.8 SEQ. ID NO. 186 OGS 1038 Reverse primer for SEQ ID NO. 8 SEQ. ID NO.187 OGS 1045 Forward primer for SEQ ID NO. 9 SEQ. ID NO. 188 OGS 1046Reverse primer for SEQ ID NO. 9 SEQ. ID NO. 189 OGS 1240 Forward primerfor SEQ ID NO. 10 SEQ. ID NO. 190 OGS 1241 Reverse primer for SEQ ID NO.10 SEQ. ID NO. 191 OGS 1304 Forward primer for SEQ ID NO. 11 SEQ. ID NO.192 OGS 1305 Reverse primer for SEQ ID NO. 11 SEQ. ID NO. 193 OGS 1039Forward primer for SEQ ID NO. 12 SEQ. ID NO. 194 OGS 1040 Reverse primerfor SEQ ID NO. 12 SEQ. ID NO. 195 OGS 1095 Forward primer for SEQ ID NO.13 SEQ. ID NO. 196 OGS 1096 Reverse primer for SEQ ID NO. 13 SEQ. ID NO.197 OGS 1284 Forward primer for SEQ ID NO. 15 SEQ. ID NO. 198 OGS 1285Reverse primer for SEQ ID NO. 15 SEQ. ID NO. 199 OGS 1063 Forward primerfor SEQ ID NO. 16 SEQ. ID NO. 200 OGS 1064 Reverse primer for SEQ ID NO.16 SEQ. ID NO. 201 OGS 1031 Forward primer for SEQ ID NO. 17 SEQ. ID NO.202 OGS 1032 Reverse primer for SEQ ID NO. 17 SEQ. ID NO. 203 OGS 1308Forward primer for SEQ ID NO. 18 SEQ. ID NO. 204 OGS 1309 Reverse primerfor SEQ ID NO. 18 SEQ. ID NO. 205 OGS 1069 Forward primer for SEQ ID NO.19 SEQ. ID NO. 206 OGS 1070 Reverse primer for SEQ ID NO. 19 SEQ. ID NO.207 OGS 1061 Forward primer for SEQ ID NO. 20 SEQ. ID NO. 208 OGS 1062Reverse primer for SEQ ID NO. 20 SEQ. ID NO. 209 OGS 1097 Forward primerfor SEQ ID NO. 21 SEQ. ID NO. 210 OGS 1098 Reverse primer for SEQ ID NO.21 SEQ. ID NO. 211 OGS 1075 Forward primer for SEQ ID NO. 22 SEQ. ID NO.212 OGS 1076 Reverse primer for SEQ ID NO. 22 SEQ. ID NO. 213 OGS 1232Forward primer for SEQ ID NO. 23 SEQ. ID NO. 214 OGS 1233 Reverse primerfor SEQ ID NO. 23 SEQ. ID NO. 215 OGS 1067 Forward primer for SEQ ID NO.24 SEQ. ID NO. 216 OGS 1068 Reverse primer for SEQ ID NO. 24 SEQ. ID NO.217 OGS 1099 Forward primer for SEQ ID NO. 25 SEQ. ID NO. 218 OGS 1100Reverse primer for SEQ ID NO. 25 SEQ. ID NO. 219 OGS 1246 Forward primerfor SEQ ID NO. 26 SEQ. ID NO. 220 OGS 1247 Reverse primer for SEQ ID NO.26 SEQ. ID NO. 221 OGS 1093 Forward primer for SEQ ID NO. 27 SEQ. ID NO.222 OGS 1094 Reverse primer for SEQ ID NO. 27 SEQ. ID NO. 223 OGS 1332Forward primer for SEQ ID NO. 28 SEQ. ID NO. 224 OGS 1333 Reverse primerfor SEQ ID NO. 28 SEQ. ID NO. 225 OGS 1101 Forward primer for SEQ ID NO.29 SEQ. ID NO. 226 OGS 1102 Reverse primer for SEQ ID NO. 29 SEQ. ID NO.227 OGS 1300 Forward primer for SEQ ID NO. 30 SEQ. ID NO. 228 OGS 1301Reverse primer for SEQ ID NO. 30 SEQ. ID NO. 229 OGS 1302 Forward primerfor SEQ ID NO. 31 SEQ. ID NO. 230 OGS 1303 Reverse primer for SEQ ID NO.31 SEQ. ID NO. 231 OGS 1292 Forward primer for SEQ ID NO. 33 SEQ. ID NO.232 OGS 1294 Reverse primer for SEQ ID NO. 33 SEQ. ID NO. 233 OGS 1242Forward primer for SEQ ID NO. 34 SEQ. ID NO. 234 OGS 1243 Reverse primerfor SEQ ID NO. 34 SEQ. ID NO. 235 OGS 1280 Forward primer for SEQ ID NO.36 SEQ. ID NO. 236 OGS 1281 Reverse primer for SEQ ID NO. 36 SEQ. ID NO.237 OGS 1159 Forward primer for SEQ ID NO. 37 SEQ. ID NO. 238 OGS 1160Reverse primer for SEQ ID NO. 37 SEQ. ID NO. 239 OGS 1310 Forward primerfor SEQ ID NO. 39 SEQ. ID NO. 240 OGS 1311 Reverse primer for SEQ ID NO.39 SEQ. ID NO. 241 OGS 1155 Forward primer for SEQ ID NO. 40 SEQ. ID NO.242 OGS 1156 Reverse primer for SEQ ID NO. 40 SEQ. ID NO. 243 OGS 1316Forward primer for SEQ ID NO. 42 SEQ. ID NO. 244 OGS 1317 Reverse primerfor SEQ ID NO. 42 SEQ. ID NO. 245 OGS 1306 Forward primer for SEQ ID NO.43 SEQ. ID NO. 246 OGS 1307 Reverse primer for SEQ ID NO. 43 SEQ. ID NO.247 OGS 1286 Forward primer for SEQ ID NO. 46 SEQ. ID NO. 248 OGS 1287Reverse primer for SEQ ID NO. 46 SEQ. ID NO. 249 OGS 1244 Forward primerfor SEQ ID NO. 47 SEQ. ID NO. 250 OGS 1245 Reverse primer for SEQ ID NO.47 SEQ. ID NO. 251 OGS 1035 Forward primer for SEQ ID NO. 50 SEQ. ID NO.252 OGS 1036 Reverse primer for SEQ ID NO. 50 SEQ. ID NO. 253 OGS 1248Forward primer for SEQ ID NO. 51 SEQ. ID NO. 254 OGS 1249 Reverse primerfor SEQ ID NO. 51

TABLE 4 Nucleotide and amino acid sequences of the SEQ. ID NOs.Nucleotide Sequence (5′-3′) ORFs SEQ.ID NO. 1 SEQ.ID NO. 51 STAR clone:MPVINIEDLTEKDKLKMEVDQLKKEVCTGGAAGCTGAAGAATCACCGGCTTCAGTGACATGGAACCCAGCGATTTGATTTTTGACGAGTATCGTLERMLVSKCCEEVRDYVEERSGEDPGGTGACTTTGAGGTGGTCAAGAAACCACACTTTAAGAACAATGTCCA LVKGIPEDKNPFKELKGGCVISNM_021955:AATCATATTAGTGAAGATTAGGAAGAAGCTTTAAAATCCCAAGGCTAGTGTGCATTGCTAGAATTGTTAAGAGAGAGAGCTCATATGAAATTGGTTATCGTGGGATATTTAAAATAAAACAAAGAACAGTTTACTTTCAGGCAAAAAGATGCCAGTAATCAATATTGAGGACCTGACAGAAAAGGACAAATTGAAGATGGAAGTTGACCAGCTCAAGAAAGAAGTGACACTGGAAAGAATGCTAGTTTCCAAATGTTGTGAAGAAGTAAGAGATTACGTTGAAGAACGATCTGGCGAGGATCCACTGGTAAAGGGCATCCCAGAGGACAAAAATCCCTTCAAGGAGCTCAAAGGAGGCTGTGTGATTTCATAATACAAACAAAAAGAAAAAAAATTAAACAAATTCTTGGAAATATCTCAAATGTTAATAACAATATGAATTTTTCTCATGCATACTATTACTACTAAGCATGTACGTGAATTTTTAAATTTATAGATGTAAACTTTTAATAAAAATTGGGGTGTGGTAACCCATCATTCTATGTTTTTCTTAACATAGCTGGCACAGGGTTTAACACATAATTGCCAATAAATATTGCTTAAAGTTCTTTAAAAAGAACTATGTTTT SEQ.ID NO. 2 SEQ.ID NO. 52GCACGAGGAAGCCACAGATCTCTTAAGAACTTTCTGTCTCCAAACCGTGGCTGCTCGATAAATCAGAMVERCSRQGCTITMAYIDYNMIVAFMCAGAACAGTTAATCCTCAATTTAAGCCTGATCTAACCCCTAGAAACAGATATAGAACAATGGAAGTGLGNYINLRESSTEPNDSLWFSLQKKNACAACAAGATTGACATGGAATGATGAAAATCATCTGCGCAACTGCTTGGAAATGTTTCTTTGAGTCTDTTEIETLLLNTAPKIIDEQLVCRLSTCTCTATAAGTCTAGTGTTCATGGAGGTAGCATTGAAGATATGGTTGAAAGATGCAGCCGTCAGGGAKTDIFIICRDNKIYLDKMITRNLKLRTGTACTATAACAATGGCTTACATTGATTACAATATGATTGTAGCCTTTATGCTTGGAAATTATATTAFYGHRQYLECEVERVEGIKDNLDDIKATTTACGTGAAAGTTCTACAGAGCCAAATGATTCCCTATGGTTTTCACTTCAAAAGAAAAATGACACRIIKAREHRNRLLADIRDYRPYADLVCACTGAAATAGAAACTTTACTCTTAAATACAGCACCAAAAATTATTGATGAGCAACTGGTGTGTCGTSEIRILLVGPVGSGKSSFFNSVKSIFTTATCGAAAACGGATATTTTCATTATATGTCGAGATAATAAAATTTATCTAGATAAAATGATAACAAHGHVTGQAVVGSDTTSITERYRIYSVGAAACTTGAAACTAAGGTTTTATGGCCACCGTCAGTATTTGGAATGTGAAGTTTTTCGAGTTGAAGGKDGKNGKSLPFMLCDTMGLDGAEGAGAATTAAGGATAACCTAGACGACATAAAGAGGATAATTAAAGCCAGAGAGCACAGAAATAGGCTTCTALCMDDIPHILKGCMPDRYQFNSRKPIGCAGACATCAGAGACTATAGGCCCTATGCAGACTTGGTTTCAGAAATTCGTATTCTTTTGGTGGGTCTPEHSTFITSPSLKDRIHCVAYVLDICAGTTGGGTCTGGAAAGTCCAGTTTTTTCAATTCAGTCAAGTCTATTTTTCATGGCCATGTGACTGGNSIDNLYSKMLAKVKQVHKEVLNCGICCAAGCCGTAGTGGGGTCTGATACCACCAGCATAACCGAGCGGTATAGGATATATTCTGTTAAAGATAYVALLTKVDDCSEVLQDNFLNMSRSGGAAAAAATGGAAAATCTCTGCCATTTATGTTGTGTGACACTATGGGGCTAGATGGGGCAGAAGGAGMTSQSRVMNVHKMLGIPISNILMVGNCAGGACTGTGCATGGATGACATTCCCCACATCTTAAAAGGTTGTATGCCAGACAGATATCAGTTTAAYASDLELDPMKDILILSALRQMLRAATTCCCGTAAACCAATTACACCTGAGCATTCTACTTTTATCACCTCTCCATCTCTGAAGGACAGGATTDDFLEDLPLEETGAIERALQPCICACTGTGTGGCTTATGTCTTAGACATCAACTCTATTGACAATCTCTACTCTAAAATGTTGGCAAAAGTGAAGCAAGTTCACAAAGAAGTATTAAACTGTGGTATAGCATATGTGGCCTTGCTTACTAAAGTGGATGATTGCAGTGAGGTTCTTCAAGACAACTTTTTAAACATGAGTAGATCTATGACTTCTCAAAGCCGGGTCATGAATGTCCATAAAATGCTAGGCATTCCTATTTCCAATATTTTGATGGTTGGAAATTATGCTTCAGATTTGGAACTGGACCCCATGAAGGATATTCTCATCCTCTCTGCACTGAGGCAGATGCTGCGGGCTGCAGATGATTTTTTAGAAGATTTGCCTCTTGAGGAAACTGGTGCAATTGAGAGAGCGTTACAGCCCTGCATTTGAGATAAGTTGCCTTGATTCTGACATTTGGCCCAGCCTGTACTGGTGTGCCGCAATGAGAGTCAATCTCTATTGACAGCCTGCTTCAGATTTTGCTTTTGTTCGTTTTGCCTTCTGTCCTTGGAACAGTCATATCTCAAGTTCAAAGGCCAAAACCTGAGAAGCGGTGGGCTAAGATAGGTCCTACTGCAAACCACCCCTCCATATTTCCGTACCATTTACAATTCAGTTTCTGTGACATCTTTTTAAACCACTGGAGGAAAAATGAGATATTCTCTAATTTATTCTTCTATAACACTCTATATAGAGCTATGTGAGTACTAATCACATTGAATAATAGTTATAAAATTATTGTATAGACATCTGCTTCTTAAACAGATTGTGAGTTCTTTGAGAAACAGCGTGGATTTTACTTATCTGTGTATTCACAGAGCTTAGCACAGTGCCTGGTAATGAGCAAGCATACTTGCCATTACTTTTCCTTCCCACTCTCTCCAACATCACATTCACTTTAAATTTTTCTGTATATAGAAAGGAAAACTAGCCTGGGCAACATGATGAAACCCCATCTCCACTGC SEQ.ID NO. 3SEQ.ID NO. 53GCCGAGCGGAGAGGCCGCCCATTGGCCGGCCAGCGCCACGTGGCCGCCCCCGCCGGTATATTAGGCCMSSYLEYVSCSSSGGVGGDVLSLAPKACTATTTACCTCCGGCTCACTCGCCATGGGTTGGAGAGGGCAGCTCGGGTAGAGAGGGCTGGCGGAGFCRSDARPVALQPAFPLGNGDGAFVSCGGCGCAGACGGCGGCAGTCCTGCTCAGCCTCTGCCCGGCTCCGTACTCCGGCCCCGGCCTGCGCCCCLPLAAARPSPSPPAAPARPSVPPPATCAGAAAGGTGGGGCCCGAACCATGAGCTCCTACCTGGAGTACGTGTCATGCAGCAGCAGCGGCGGGAPQYAQCTLEGAYEPGAAPAAAAGGAGTCGGCGGCGACGTGCTCAGCTTGGCACCCAAGTTCTGCCGCTCCGACGCCCGGCCCGTGGCTCTGCDYGFLGSGPAYDFPGVLGRAADDGGSAGCCCGCCTTCCCTCTGGGCAACGGCGACGGCGCCTTCGTCAGCTGTCTGCCCCTGGCCGCCGCCCGHVHYATSAVFSGGGSFLLSGQVDYAAACCCTCGCCTTCGCCCCCGGCCGCCCCCGCGCGGCCGTCCGTACCGCCTCCGGCCGCGCCCCAGTACFGEPGPFPACLKASADGHPGAFQTASGCGCAGTGCACCCTGGAGGGGGCCTACGAACCTGGTGCCGCACCTGCCGCGGCAGCTGGGGGCGCGGPAPGTYPKSVSPASGLPAAFSTFEWMACTACGGCTTCCTGGGGTCCGGGCCGGCGTACGACTTCCCGGGCGTGCTGGGGCGGGCGGCCGACGAKVKRNASKKGKLAEYGAASPSSAIRTCGGCGGGTCTCACGTCCACTACGCCACCTCGGCCGTCTTCTCGGGCGGCGGCTCTTTCCTCCTCAGCNFSTKQLTELEKEFHFNKYLTRARRIGGCCAGGTGGATTACGCGGCCTTCGGCGAACCCGGCCCTTTTCCGGCTTGTCTCAAAGCGTCAGCCGEIANCLHLNDTQVKIWFQNRRMKQKKACGGCCACCCTGGTGCTTTCCAGACCGCATCCCCGGCCCCAGGCACCTACCCCAAGTCCGTCTCTCCREREGLLATAIPVAPLQLPLSGTTPTCGCCTCCGGCCTCCCTGCCGCCTTCAGCACGTTCGAGTGGATGAAAGTGAAGAGGAATGCCTCTAAGKFIKNPGSPSQSQEPSAAAGGTAAACTCGCCGAGTATGGGGCCGCTAGCCCCTCCAGCGCGATCCGCACGAATTTCAGCACCAAGCAACTGACAGAACTGGAAAAAGAGTTTCATTTCAATAAGTACTTAACTCGAGCCCGGCGCATCGAGATAGCCAACTGCTTGCACCTGAATGACACGCAAGTCAAAATCTGGTTCCAGAACCGCAGGATGAAACAGAAGAAAAGGGAACGAGAAGGGCTTCTGGCCACGGCCATTCCTGTGGCTCCCCTCCAACTTCCCCTCTCTGGAACAACCCCCACTAAGTTTATCAAGAACCCCGGCAGCCCTTCTCAGTCCCAAGAGCCTTCGTGAGGCCGGTACTTGGGGCCGAAAAACTGTGGCCTGCAGAAGTCCCAGGCGACCCCCATCCCTATCTAGACTTAGGAGCTCAGTTTGGGATGGAGGTGGGAGAACAAAAATGAATAGGGATTTCACTTGGGAAATGAAGTACTTTAGTTGGCTTCCGAGTTCCAGACTATATGTCCAGATATTAATTGACTGTCTTGTAAGCCACTTGTTTGGTTATGATTTGTGTCTTATCAGGGAAAAGGTGCCCAGCTGCCAGCCCAGCTCCGCTGCTATCTTTGCCTCACTTAGTCATGTGCAATTCGCGTTGCAGAGTGGCAGACCATTAGTTGCTGAGTTCTGTCAGCACTCTGATGTGCTCAGAAGAGCACCTGCCCAAAGTTTTTCTGGTTTTAATTTAAAGGACAAGGCTACATATATTCAGCTTTTTGAGATGACCAAAGCTAGTTAGGGTCTCCTTGATGTAGCTAAGCTGCTTCAGTGATCTTCACATTTGCACTCCAGTTTTTTTTTCTTTAAAAAAGCGGTTTCTACCTCTCTATGTGCCTGAGTGATGATACAATCGCTGTTTAGTTACTAGATGAACAAATCCACAGAATGGGTAAAGAGTAGAATCTGAACTATATCTTGACAAATATTATTCAAACTTGAATGTAAATATATACAGTATGTATATTTTTTAAAAAGATTTGCTTGCAATGACCTTATAAGTGACATTTAATGTCATAGCATGTAAAGGGTTTTTTTTGTAATAAAAATTATAGAATCTGCAAAAAAAAAAAAAAAA SEQ.ID NO. 4SEQ.ID NO. 54CAGCCTCCAGAGCACCAGCACTGGCACTGGCACTGGCACACGCTATGGCAAATGAAGTGCAAGACCTMANEVQDLLSPRKGGHPPAVKAGGMRGCTCTCCCCTCGGAAAGGGGGACATCCTCCTGCAGTAAAAGCTGGAGGAATGAGAATTTCCAAAAAAISKKQEIGTLERHTKKTGFEKTSAIACAAGAAATTGGCACCTTGGAAAGACATACCAAAAAAACAGGATTCGAGAAAACAAGTGCCATTGCAANVAKIQTLDALNDTLEKLNYKFPATVATGTTGCCAAAATACAGACACTGGATGCCCTGAATGACACACTGGAGAAGCTCAACTATAAATTTCCHMAHQKPTPALEKVVPLKRIYIIQQPAGCAACAGTGCACATGGCACATCAAAAACCCACACCTGCTCTGGAAAAGGTTGTTCCACTGAAAAGG RKCATCTACATTATTCAGCAGCCTCGAAAATGTTAAGCCTGGATTTAAAACACAGCCGTCTGGCCAGCTGCCTCGAATATCTGACAGCTTAGCAAAAAGGGCCAAAGCTTTCCATAGGCGTGCTGCACTTGCTTGGTAAATTAAACAGCTTTTGTATCTTCCCCTTTGACTTTAGGTAATAAAGCATCCAAACTTGTAAAAAAA AAASEQ.ID NO. 5 SEQ.ID NO. 55GTAACTGAAAATCCACAAGACAGAATAGCCAGATCTCAGAGGAGCCTGGCTAAGCAAAACCCTGCAGMSTNGDDHQVKDSLEQLRCHFTWELSAACGGCTGCCTAATTTACAGCAACCATGAGTACAAATGGTGATGATCATCAGGTCAAGGATAGTCTGIDDDEMPDLENRVLDQIEFLDTKYSVGAGCAATTGAGATGTCACTTTACATGGGAGTTATCCATTGATGACGATGAAATGCCTGATTTAGAAAGIHNLLAYVKHLKGQNEEALKSLKEAACAGAGTCTTGGATCAGATTGAATTCCTAGACACCAAATACAGTGTGGGAATACACAACCTACTAGCENLMQEEHDNQANVRSLVTWGNFAWMCTATGTGAAACACCTGAAAGGCCAGAATGAGGAAGCCCTGAAGAGCTTAAAAGAAGCTGAAAACTTAYYHMGRLAEAQTYLDKVENICKKLSNATGCAGGAAGAACATGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTGGGGCAACTTTGCCTGGAPFRYRMECPEIDCEEGWALLKCGGKNTGTATTACCACATGGGCAGACTGGCAGAAGCCCAGACTTACCTGGACAAGGTGGAGAACATTTGCAAYERAKACFEKVLEVDPENPESSAGYAGAAGCTTTCAAATCCCTTCCGCTATAGAATGGAGTGTCCAGAAATAGACTGTGAGGAAGGATGGGCCISAYRLDGFKLATKNHKPFSLLPLRQTTGCTGAAGTGTGGAGGAAAGAATTATGAACGGGCCAAGGCCTGCTTTGAAAAGGTGCTTGAAGTGGAVRLNPDNGYIKVLLALKLQDEGQEAACCCTGAAAACCCTGAATCCAGCGCTGGGTATGCGATCTCTGCCTATCGCCTGGATGGCTTTAAATTEGEKYIEEALANMSSQTYVFRYAAKFAGCCACAAAAAATCACAAGCCATTTTCTTTGCTTCCCCTAAGGCAGGCTGTCCGCTTAAATCCAGACYRRKGSVDKALELLKKALQETPTSVLAATGGATATATTAAGGTTCTCCTTGCCCTGAAGCTTCAGGATGAAGGACAGGAAGCTGAAGGAGAAALHHQIGLCYKAQMIQIKEATKGQPRGAGTACATTGAAGAAGCTCTAGCCAACATGTCCTCACAGACCTATGTCTTTCGATATGCAGCCAAGTTQNREKLDKMIRSAIFHFESAVEKKPTTTACCGAAGAAAAGGCTCTGTGGATAAAGCTCTTGAGTTATTAAAAAAGGCCTTGCAGGAAACACCCFEVAHLDLARMYIEAGNHRKAEENFQACTTCTGTCTTACTGCATCACCAGATAGGGCTTTGCTACAAGGCACAAATGATCCAAATCAAGGAGGKLLCMKPVVEETMQDIHFHYGRFQEFCTACAAAAGGGCAGCCTAGAGGGCAGAACAGAGAAAAGCTAGACAAAATGATAAGATCAGCCATATTQKKSDVNAIIHYLKAIKIEQASLTRDTCATTTTGAATCTGCAGTGGAAAAAAAGCCCACATTTGAGGTGGCTCATCTAGACCTGGCAAGAATGKSINSLKKLVLRKLRRKALDLESLSLTATATAGAAGCAGGCAATCACAGAAAAGCTGAAGAGAATTTTCAAAAATTGTTATGCATGAAACCAGLGFVYKLEGNMNEALEYYERALRLAATGGTAGAAGAAACAATGCAAGACATACATTTCCACTATGGTCGGTTTCAGGAATTTCAAAAGAAATCDFENSVRQGPTGACGTCAATGCAATTATCCATTATTTAAAAGCTATAAAAATAGAACAGGCATCATTAACAAGGGATAAAAGTATCAATTCTTTGAAGAAATTGGTTTTAAGGAAACTTCGGAGAAAGGCATTAGATCTGGAAAGCTTGAGCCTCCTTGGGTTCGTCTACAAATTGGAAGGAAATATGAATGAAGCCCTGGAGTACTATGAGCGGGCCCTGAGACTGGCTGCTGACTTTGAGAACTCTGTGAGACAAGGTCCTTAGGCACCCAGATATCAGCCACTTTCACATTTCATTTCATTTTATGCTAACATTTACTAATCATCTTTTCTGCTTACTGTTTTCAGAAACATTATAATTCACTGTAATGATGTAATTCTTGAATAATAAATCTGACAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 6 SEQ.ID NO. 56CCCGCGAGCGTCCATCCATCTGTCCGGCCGACTGTCCAGCGAAAGGGGCTCCAGGCCGGGCGCACGTMQSCARAWGLRLGRGVGGGRRLAGGSCGACCCGGGGGACCGAGGCCAGGAGAGGGGCCAAGAGCGCGGCTGACCCTTGCGGGCCGGGGCAGGGGPCWAPRSRDSSSGGGDSAAAGASRLGACGGTGGCCGCGGCCATGCAGTCCTGTGCCAGGGCGTGGGGGCTGCGCCTGGGCCGCGGGGTCGGGLERLLPRHDDFARRHIGPGDKDQREMGGCGGCCGCCGCCTGGCTGGGGGATCGGGGCCGTGCTGGGCGCCGCGGAGCCGGGACAGCAGCAGTGLQTLGLASIDELIEKTVPANIRLKRPGCGGCGGGGACAGCGCCGCGGCTGGGGCCTCGCGCCTCCTGGAGCGCCTTCTGCCCAGACACGACGALKMEDPVCENEILATLHAISSKNQIWCTTCGCTCGGAGGCACATCGGCCCTGGGGACAAAGACCAGAGAGAGATGCTGCAGACCTTGGGGCTGRSYIGMGYYNCSVPQTILRNLLENSGGCGAGCATTGATGAATTGATCGAGAAGACGGTCCCTGCCAACATCCGTTTGAAAAGACCCTTGAAAAWITQYTPYQPEVSQGRLESLLNYQTMTGGAAGACCCTGTTTGTGAAAATGAAATCCTTGCAACTCTGCATGCCATTTCAAGCAAAAACCAGATVCDITGLDMANASLLDEGTAAAEALQCTGGAGATCGTATATTGGCATGGGCTATTATAACTGCTCAGTGCCACAGACGATTTTGCGGAACTTALCYRHNKRRKFLVDPRCHPQTIAVVQCTGGAGAACTCAGGATGGATCACCCAGTATACTCCATACCAGCCTGAGGTGTCTCAGGGGAGGCTGGTRAKYTGVLTELKLPCEMDFSGKDVSAGAGTTTACTCAACTACCAGACCATGGTGTGTGACATCACAGGCCTGGACATGGCCAATGCATCCCTGVLFQYPDTEGKVEDFTELVERAHQSGCTGGATGAGGGGACTGCAGCCGCAGAGGCACTGCAGCTGTGCTACAGACACAACAAGAGGAGGAAAGSLACCATDLLALCILRPPGEFGVDITTTCTCGTTGATCCCCGTTGCCACCCACAGACAATAGCTGTTGTCCAGACTCGAGCCAAATATACTGALGSSQRFGVPLGYGGPHAAFFAVREGAGTCCTCACTGAGCTGAAGTTACCCTGTGAAATGGACTTCAGTGGAAAAGATGTCAGTGGAGTGTTSLVRMMPGRMVGVTRDATGKEVYRLAGTTCCAGTACCCAGACACGGAGGGGAAGGTGGAAGACTTTACGGAACTCGTGGAGAGAGCTCATCAGLQTREQHIRRDKATSNICTAQALLANAGTGGGAGCCTGGCCTGCTGTGCTACTGACCTTTTAGCTTTGTGCATCTTGAGGCCACCTGGAGAATMAAMFRIYHGSHGLEHIARRVHNATLTTGGGGTAGACATCGCCCTGGGCAGCTCCCAGAGATTTGGAGTGCCACTGGGCTATGGGGGACCCCAILSEGLKRAGHQLQHDLFFDTLKIHCTGCAGCATTTTTTGCTGTCCGAGAAAGCTTGGTGAGAATGATGCCTGGAAGAATGGTGGGGGTAACAGCSVKEVLGRAAQRQINFRLFEDGTLAGAGATGCCACTGGGAAAGAAGTGTATCGTCTTGCTCTTCAAACCAGGGAGCAACACATTCGGAGAGGISLDETVNEKDLDDLLWIFGCESSAACAAGGCTACCAGCAACATCTGTACAGCTCAGGCCCTCTTGGCGAATATGGCTGCCATGTTTCGAATELVAESMGEECRGIPGSVFKRTSPFLCTACCATGGTTCCCATGGGCTGGAGCATATTGCTAGGAGGGTACATAATGCCACTTTGATTTTGTCATHQVFNSYHSETNIVRYMKKLENKDIGAAGGTCTCAAGCGAGCAGGGCATCAACTCCAGCATGACCTGTTCTTTGATACCTTGAAGATTCATTSLVHSMIPLGSCTMKLNSSSELAPITGTGGCTGCTCAGTGAAGGAGGTCTTGGGCAGGGCGGCTCAGCGGCAGATCAATTTTCGGCTTTTTGAWKEFANIHPFVPLDQAQGYQQLFRELGGATGGCACACTTGGTATTTCTCTTGATGAAACAGTCAATGAAAAAGATCTGGACGATTTGTTGTGGEKDLCELTGYDQVCFQPNSGAQGEYAATCTTTGGTTGTGAGTCATCTGCAGAACTGGTTGCTGAAAGCATGGGAGAGGAGTGCAGAGGTATTCGLATIRAYLNQKGEGHRTVCLIPKSACAGGGTCTGTGTTCAAGAGGACCAGCCCGTTCCTCACCCATCAAGTGTTCAACAGCTACCACTCTGAHGTNPASAHMAGMKIQPVEVDKYGNIAACAAACATTGTCCGGTACATGAAGAAACTGGAAAATAAAGACATTTCCCTTGTTCACAGCATGATTDAVHLKAMVDKHKENLAAIMITYPSTCCACTGGGATCCTGCACCATGAAACTGAACAGTTCGTCTGAACTCGCACCTATCACATGGAAAGAATNGVFEENISDVCDLIHQHGGQVYLDGTTGCAAACATCCACCCCTTTGTGCCTCTGGATCAAGCTCAAGGATATCAGCAGCTTTTCCGAGAGCTANMNAQVGICRPGDFGSDVSHLNLHKTGAGAAGGATTTGTGTGAACTCACAGGTTATGACCAGGTCTGTTTCCAGCCAAACAGCGGAGCCCAGTFCIPHGGGGPGMGPIGVKKHLAPFLGGAGAATATGCTGGACTGGCCACTATCCGAGCCTACTTAAACCAGAAAGGAGAGGGGCACAGAACGGPNHPVISLKRNEDACPVGTVSAAPWGTTTGCCTCATTCCGAAATCAGCACATGGGACCAACCCAGCAAGTGCCCACATGGCAGGCATGAAGATSSSILPISWAYIKMMGGKGLKQATETTCAGCCTGTGGAGGTGGATAAATATGGGAATATCGATGCAGTTCACCTCAAGGCCATGGTGGATAAGAlLNANYMAKRLETHYRILFRGARGYCACAAGGAGAACCTAGCAGCTATCATGATTACATACCCATCCACCAATGGGGTGTTTGAAGAGAACAVGHEFILDTRPFKKSANIEAVDVAKRTCAGTGACGTGTGTGACCTCATCCATCAACATGGAGGACAGGTCTACCTAGACGGGGCAAATATGAALQDYGFHAPTMSWPVAGTLMVEPTESTGCTCAGGTGGGAATCTGTCGCCCTGGAGACTTCGGGTCTGATGTCTCGCACCTAAATCTTCACAAGEDKAELDRFCDAMISIRQEIADIEEGACCTTCTGCATTCCCCACGGAGGAGGTGGTCCTGGCATGGGGCCCATCGGAGTGAAGAAACATCTCGRIDPRVNPLKMSPHSLTCVTSSHWDRCCCCGTTTTTGCCCAATCATCCCGTCATTTCACTAAAGCGGAATGAGGATGCCTGTCCTGTGGGAACPYSREVAAFPLPFMKPENKFWPTIARCGTCAGTGCGGCCCCATGGGGCTCCAGTTCCATCTTGCCCATTTCCTGGGCTTATATCAAGATGATGIDDIYGDQHLVCTCPPMEVYESPFSEGGAGGCAAGGGTCTTAAACAAGCCACGGAAACTGCGATATTAAATGCCAACTACATGGCCAAGCGATQKRASSTAGAAACACACTACAGAATTCTTTTCAGGGGTGCAAGAGGTTATGTGGGTCATGAATTTATTTTGGACACGAGACCCTTCAAAAAGTCTGCAAATATTGAGGCTGTGGATGTGGCCAAGAGACTCCAGGATTATGGATTTCACGCCCCTACCATGTCCTGGCCTGTGGCAGGGACCCTCATGGTGGAGCCCACTGAGTCGGAGGACAAGGCAGAGCTGGACAGATTCTGTGATGCCATGATCAGCATTCGGCAGGAAATTGCTGACATTGAGGAGGGCCGCATCGACCCCAGGGTCAATCCGCTGAAGATGTCTCCACACTCCCTGACCTGCGTTACATCTTCCCACTGGGACCGGCCTTATTCCAGAGAGGTGGCAGCATTCCCACTCCCCTTCATGAAACCAGAGAACAAATTCTGGCCAACGATTGCCCGGATTGATGACATATATGGAGATCAGCACCTGGTTTGTACCTGCCCACCCATGGAAGTTTATGAGTCTCCATTTTCTGAACAAAAGAGGGCGTCTTCTTAGTCCTCTCTCCCTAAGTTTAAAGGACTGATTTGATGCCTCTCCCCAGAGCATTTGATAAGCAAGAAAGATTTCATCTCCCACCCCAGCCTCAAGTAGGAGTTTTATATACTGTGTATATCTCTGTAATCTCTGTCAAGGTAAATGTAAATACAGTAGCTGGAGGGAGTCGAAGCTGATGGTTGGAAGACGGATTTGCTTTGGTATTCTGCTTCCACATGTGCCAGTTGCCTGGATTGGGAGCCATTTTGTGTTTTGCGTAGAAAGTTTTAGGAACTTTAACTTTTAATGTGGCAAGTTTGCAGATGTCATAGAGGCTATCCTGGAGACTTAATAGACATTTTTTTGTTCCAAAAGAGTCCATGTGGACTGTGCCATCTGTGGGAAATCCCAGGGCAAATGTTTACATTTTGTATACCCTGAAGAACTCTTTTTCCTCTAATATGCCTAATCTGTAATCACATTTCTGAGTGTTTTCCTCTTTTTCTGTGTGAGGTTTTTTTTTTTTTTAATCTGCATTTATTAGTATTCTAATAAAAGCATTTTGATCGGAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 7 SEQ.ID NO. 57GGGTCGTCATGATCCGGACCCCATTGTCGGCCTCTGCCCATCGCCTGCTCCTCCCAGGCTCCCGCGGMIRTPLSASAHRLLLPGSRGRPPRNMCCGACCCCCGCGCAACATGCAGCCCACGGGCCGCGAGGGTTCCCGCGCGCTCAGCCGGCGGTATCTGQPTGREGSRALSRRYLRRLLLLLLLLCGGCGTCTGCTGCTCCTGCTACTGCTGCTGCTGCTGCGGCAGCCCGTAACCCGCGCGGAGACCACGCLLRQPVTRAETTPGAPRALSTLGSPSCGGGCGCCCCCAGAGCCCTCTCCACGCTGGGCTCCCCCAGCCTCTTCACCACGCCGGGTGTCCCCAGLFTTPGVPSALTTPGLTTPGTPKTLDCGCCCTCACTACCCCAGGCCTCACTACGCCAGGCACCCCCAAAACCCTGGACCTTCGGGGTCGCGCGLRGRAQALMRSFPLVDGHNDLPQVLRCAGGCCCTGATGCGGAGTTTCCCACTCGTGGACGGCCACAATGACCTGCCCCAGGTCCTGAGACAGCQRYKNVLQDVNLRNFSHGQTSLDRLRGTTACAAGAATGTGCTTCAGGATGTTAACCTGCGAAATTTCAGCCATGGTCAGACCAGCCTGGACAGDGLVGAQFWSASVSCQSQDQTAVRLAGCTTAGAGACGGCCTCGTGGGTGCCCAGTTCTGGTCAGCCTCCGTCTCATGCCAGTCCCAGGACCAGLEQIDLIHRMCASYSELELVTSAEGLACTGCCGTGCGCCTCGCCCTGGAGCAGATTGACCTCATTCACCGCATGTGTGCCTCCTACTCTGAACNSSQKLACLIGVEGGHSLDSSLSVLRTCGAGCTTGTGACCTCAGCTGAAGGTCTGAACAGCTCTCAAAAGCTGGCCTGCCTCATTGGCGTGGASFYVLGVRYLTLTFTCSTPWAESSTKGGGTGGTCACTCACTGGACAGCAGCCTCTCTGTGCTGCGCAGTTTCTATGTGCTGGGGGTGCGCTACFRHHMYTNVSGLTSFGEKVVEELNRLCTGACACTTACCTTCACCTGCAGTACACCATGGGCAGAGAGTTCCACCAAGTTCAGACACCACATGTGMMIDLSYASDTLIRRVLEVSQAPVIACACCAACGTCAGCGGATTGACAAGCTTTGGTGAGAAAGTAGTAGAGGAGTTGAACCGCCTGGGCATFSHSAARAVCDNLLNVPDDILQLLKKGATGATAGATTTGTCCTATGCATCGGACACCTTGATAAGAAGGGTCCTGGAAGTGTCTCAGGCTCCTNGGIVMVTLSMGVLQCNLLANVSTVAGTGATCTTCTCCCACTCAGCTGCCAGAGCTGTGTGTGACAATTTGTTGAATGTTCCCGATGATATCCDHFDHIRAVIGSEFIGIGGNYDGTGRTGCAGCTTCTGAAGAAGAACGGTGGCATCGTGATGGTGACACTGTCCATGGGGGTGCTGCAGTGCAAFPQGLEDVSTYPVLIEELLSRSWSEECCTGCTTGCTAACGTGTCCACTGTGGCAGATCACTTTGACCACATCAGGGCAGTCATTGGATCTGAGELQGVLRGNLLRVFRQVEKVREESRATTCATCGGGATTGGTGGAAATTATGACGGGACTGGCCGGTTCCCTCAGGGGCTGGAGGATGTGTCCAQSPVEAEFPYGQLSTSCHSHLVPQNGCATACCCAGTCCTGATAGAGGAGTTGCTGAGTCGTAGCTGGAGCGAGGAAGAGCTTCAAGGTGTCCTHQATHLEVTKQPTNRVPWRSSNASPYTCGTGGAAACCTGCTGCGGGTCTTCAGACAAGTGGAAAAGGTGAGAGAGGAGAGCAGGGCGCAGAGCLVPGLVAAATIPTFTQWLCCCCGTGGAGGCTGAGTTTCCATATGGGCAACTGAGCACATCCTGCCACTCCCACCTCGTGCCTCAGAATGGACACCAGGCTACTCATCTGGAGGTGACCAAGCAGCCAACCAATCGGGTCCCCTGGAGGTCCTCAAATGCCTCCCCATACCTTGTTCCAGGCCTTGTGGCTGCTGCCACCATCCCAACCTTCACCCAGTGGCTCTGCTGACACAGTCGGTCCCCGCAGAGGTCACTGTGGCAAAGCCTCACAAAGCCCCCTCTCCTAGTTCATTCACAAGCATATGCTGAGAATAAACATGTTACACATGGAAAAAAAAAAAAAAAAAAASEQ.ID NO. 8 SEQ.ID NO. 58AGTCCTGCGTCCGGGCCCCGAGGCGCAGCAGGGCACCAGGTGGAGCACCAGCTACGCGTGGCGCAGCMLRTESCRPRSPAGQVAAASPLLLLLGCAGCGTCCCTAGCACCGAGCCTCCCGCAGCCGCCGAGATGCTGCGAACAGAGAGCTGCCGCCCCAGLLLAWCAGACRGAPILPQGLQPEQQLGTCGCCCGCCGGACAGGTGGCCGCGGCGTCCCCGCTCCTGCTGCTGCTGCTGCTGCTCGCCTGGTGCQLWNEIDDTCSSFLSIDSQPQASNALGCGGGCGCCTGCCGAGGTGCTCCAATATTACCTCAAGGATTACAGCCTGAACAACAGCTACAGTTGTEELCFMIMGMLPKPQEQDEKDNTKRFGGAATGAGATAGATGATACTTGTTCGTCTTTTCTGTCCATTGATTCTCAGCCTCAGGCATCCAACGCLFHYSKTQKLGKSNVVSSVVHPLLQLACTGGAGGAGCTTTGCTTTATGATTATGGGAATGCTACCAAAGCCTCAGGAACAAGATGAAAAAGATVPHLHERRMKRFRVDEEFQSPFASQSAATACTAAAAGGTTCTTATTTCATTATTCGAAGACACAGAAGTTGGGCAAGTCAAATGTTGTGTCGTRGYFLFRPRNGRRSAGFICAGTTGTGCATCCGTTGCTGCAGCTCGTTCCTCACCTGCATGAGAGAAGAATGAAGAGATTCAGAGTGGACGAAGAATTCCAAAGTCCCTTTGCAAGTCAAAGTCGAGGATATTTTTTATTCAGGCCACGGAATGGAAGAAGGTCAGCAGGGTTCATTTAAAATGGATGCCAGCTAATTTTCCACAGAGCAATGCTATGGAATACAAAATGTACTGACATTTTGTTTTCTTCTGAAAAAAATCCTTGCTAAATGTACTCTGTTGAAAATCCCTGTGTTGTCAATGTTCTCAGTTGTAACAATGTTGTAAATGTTCAATTTGTTGAAAATTAAAAAATCTAAAAATAAA SEQ.ID NO. 9 SEQ.ID NO. 59GGGCGCAGCGGGGCCCGTCTGCAGCAAGTGACCGACGGCCGGGACGGCCGCCTGCCCCCTCTGCCACMHVRSLRAAAPHSFVALWAPLFLLRSCTGGGGCGGTGCGGGCCCGGAGCCCGGAGCCCGGGTAGCGCGTAGAGCCGGCGCGATGCACGTGCGCALADFSLDNEVHSSFIHRRLRSQERRTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCTGCTGCGCTCCGEMQREILSILGLPHRPRPHLQGKHNSCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCCTCCGCAGCCAAPMFMLDLYNAMAVEEGGGPGGQGFSGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCGCGCCCGCACYPYKAVFSTQGPPLASLQDSHFLTDACTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGCGGTGGAGGDMVMSFVNLVEHDKEFFHPRYHHREFAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCCAGGGCCCRFDLSKIPEGEAVTAAEFRIYKDYIRCCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTCGTCAACERFDNETFRISVYQVLQEHLGRESDLCTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGATCTTTFLLDSRTLWASEEGWLVFDITATSNHCCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCCGGGAWVVNPRHNLGLQLSVETLDGQSINPKACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGGGAALAGLIGRHGPQNKQPFMVAFFKATEVTCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGACAHFRSIRSTGSKQRSQNRSKTPKNQEATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGGALRMANVAENSSSDQRQACKKHELYVSGACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAACFRDLGWQDWIIAPEGYAAYYCEGECAAAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGFPLNSYMNATNHAIVQTLVHFINPETGGAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAAVPKPCCAPTQLNAISVLYFDDSSNVICGTGGCAGAGAACAGCAGCAGCGACCAGAGGCAGGCCTGTAAGAAGCACGAGCTGTATGTCAGCTTCLKKYRNMVVRACGCHCGAGACCTGGGCTGGCAGGACTGGATCATCGCGCCTGAAGGCTACGCCGCCTACTACTGTGAGGGGGAGTGTGCCTTCCCTCTGAACTCCTACATGAACGCCACCAACCACGCCATCGTGCAGACGCTGGTCCACTTCATCAACCCGGAAACGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGCCATCTCCGTCCTCTACTTCGATGACAGCTCCAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCTCCGAGAATTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTCCATTGCTCGCCTTGGCCAGGAACCAGCAGACCAACTGCCTTTTGTGAGACCTTCCCCTCCCTATCCCCAACTTTAAAGGTGTGAGAGTATTAGGAAACATGAGCAGCATATGGCTTTTGATCAGTTTTTCAGTGGCAGCATCCAATGAACAAGATCCTACAAGCTGTGCAGGCAAAACCTAGCAGGAAAAAAAAACAACGCATAAAGAAAAATGGCCGGGCCAGGTCATTGGCTGGGAAGTCTCAGCCATGCACGGACTCGTTTCCAGAGGTAATTATGAGCGCCTACCAGCCAGGCCACCCAGCCGTGGGAGGAAGGGGGCGTGGCAAGGGGTGGGCACATTGGTGTCTGTGCGAAAGGAAAATTGACCCGGAAGTTCCTGTAATAAATGTCACAATAAAACGAATGAA TGSEQ.ID NO. 10 SEQ.ID NO. 60CCGGTGAGTCGCCGGCGCTGCAGAGGGAGGCGGCACTGGTCTCGACGTGGGGCGGCCAGCGATGAAGMKPPSSIQTSEFDSSDEEPIEDEQTPCCGCCCAGTTCAATACAAACAAGTGAGTTTGACTCATCAGATGAAGAGCCTATTGAAGATGAACAGAIHISWLSLSRVNCSQFLGLCALPGCKCTCCAATTCATATATCATGGCTATCTTTGTCACGAGTGAATTGTTCTCAGTTTCTCGGTTTATGTGCFKDVRRNVQKDTEELKSCGIQDIFVFTCTTCCAGGTTGTAAATTTAAAGATGTTAGAAGAAATGTCCAAAAAGATACAGAAGAACTAAAGAGCCTRGELSKYRVPNLLDLYQQCGIITHTGTGGTATACAAGACATATTTGTTTTCTGCACCAGAGGGGAACTGTCAAAATATAGAGTCCCAAACCHHPIADGGTPDIASCCEIMEELTTCLTTCTGGATCTCTACCAGCAATGTGGAATTATCACCCATCATCATCCAATCGCAGATGGAGGGACTCCKNYRKTLIHCYGGLGRSCLVAACLLLTGACATAGCCAGCTGCTGTGAAATAATGGAAGAGCTTACAACCTGCCTTAAAAATTACCGAAAAACCYLSDTISPEQAIDSLRDLRGSGAIQTTTAATACACTGCTATGGAGGACTTGGGAGATCTTGTCTTGTAGCTGCTTGTCTCCTACTATACCTGTIKQYNYLHEFRDKLAAHLSSRDSQSRCTGACACAATATCACCAGAGCAAGCCATAGACAGCCTGCGAGACCTAAGAGGATCCGGGGCAATACA SVSRGACCATCAAGCAATACAATTATCTTCATGAGTTTCGGGACAAATTAGCTGCACATCTATCATCAAGAGATTCACAATCAAGATCTGTATCAAGATAAAGGAATTCAAATAGCATATATATGACCATGTCTGAAATGTCAGTTCTCTAGCATAATTTGTATTGAAATGAAACCACCAGTGTTATCAACTTGAATGTAAATGTACATGTGCAGATATTCCTAAAGTTTTATTGAC SEQ.ID NO. 11 SEQ.ID NO. 61AGAGCGATCATGTCGCACAAACAAATTTACTATTCGGACAAATACGACGACGAGGAGTTTGAGTATCMSHKQIYYSDKYDDEEFEYRHVMLPKGACATGTCATGCTGCCCAAGGACATAGCCAAGCTGGTCCCTAAAACCCATCTGATGTCTGAATCTGADIAKLVPKTHLMSESEWRNLGVQQSQATGGAGGAATCTTGGCGTTCAGCAGAGTCAGGGATGGGTCCATTATATGATCCATGAACCAGAACCTGWVHYMIHEPEPHILLFRRPLPKKPKCACATCTTGCTGTTCCGGCGCCCACTACCCAAGAAACCAAAGAAATGAAGCTGGCAAGCTACTTTTC KAGCCTCAAGCTTTACACAGCTGTCCTTACTTCCTAACATCTTTCTGATAACATTATTATGTTGCCTTCTTGTTTCTCACTTTGATATTTAAAAGATGTTCAATACACTGTTTGAATGTGCTGGTAACTGCTTTGCTTCTTGAGTAGAGCCACCACCACCATAGCCCAGCCAGATGAGTGCTCTGTGGACCCACAGCCTAAGCTGAGTGTGACCCCAGAAGCCACGATGTGCTCTGTATCCAGAACACACTTGGCAGATGGAGGAAGCATCTGAGTTTGAGACCATGGCTGTTACAGGGATCATGTAAACTTGCTGTTTTTGTTTTTTCTGCCGGGTGTTGTATGTGTGGTGACTTGCGGATTTATGTTTCAGTGTACTGGAAACTTTCCATTTTATTCAAGAAATCTGTTCATGTTAAAAGCCTTGATTAAAGAGGAAGTTTTTATAAT SEQ.ID NO. 12SEQ.ID NO. 62CGAGTTCCGGCGAGGCTTCAGGGTACAGCTCCCCCGCAGCCAGAAGCCGGGCCTGCAGCGCCTCAGCMERRRLWGSIQSRYISMSVWTSPRRLACCGCTCCGGGACACCCCACCCGCTTCCCAGGCGTGACCTGTCAACAGCAACTTCGCGGTGTGGTGAVELAGQSLLKDEALAIAALELLPRELACTCTCTGAGGAAAAACCATTTTGATTATTACTCTCAGACGTGCGTGGCAACAAGTGACTGAGACCTFPPLFMAAFDGRHSQTLKAMVQAWPFAGAAATCCAAGCGTTGGAGGTCCTGAGGCCAGCCTAAGTCGCTTCAAAATGGAACGAAGGCGTTTGTTCLPLGVLMKGQHLHLETFKAVLDGLGGGGTTCCATTCAGAGCCGATACATCAGCATGAGTGTGTGGACAAGCCCACGGAGACTTGTGGAGCTDVLLAQEVRPRRWKLQVLDLRKNSHQGGCAGGGCAGAGCCTGCTGAAGGATGAGGCCCTGGCCATTGCCGCCCTGGAGTTGCTGCCCAGGGAGDFWTVWSGNRASLYSFPEPEAAQPMTCTCTTCCCGCCACTCTTCATGGCAGCCTTTGACGGGAGACACAGCCAGACCCTGAAGGCAATGGTGCKKRKVDGLSTEAEQPFIPVEVLVDLFAGGCCTGGCCCTTCACCTGCCTCCCTCTGGGAGTGCTGATGAAGGGACAACATCTTCACCTGGAGACLKEGACDELFSYLIEKVKRKKNVLRLCTTCAAAGCTGTGCTTGATGGACTTGATGTGCTCCTTGCCCAGGAGGTTCGCCCCAGGAGGTGGAAACCKKLKIFAMPMQDIKMILKMVQLDSCTTCAAGTGCTGGATTTACGGAAGAACTCTCATCAGGACTTCTGGACTGTATGGTCTGGAAACAGGGIEDLEVTCTWKLPTLAKFSPYLGQMICCAGTCTGTACTCATTTCCAGAGCCAGAAGCAGCTCAGCCCATGACAAAGAAGCGAAAAGTAGATGGNLRRLLLSHIHASSYISPEKEEQYIATTTGAGCACAGAGGCAGAGCAGCCCTTCATTCCAGTAGAGGTGCTCGTAGACCTGTTCCTCAAGGAAQFTSQFLSLQCLQALYVDSLFFLRGRGGTGCCTGTGATGAATTGTTCTCCTACCTCATTGAGAAAGTGAAGCGAAAGAAAAATGTACTACGCCLDQLLRHVMNPLETLSITNCRLSEGDTGTGCTGTAAGAAGCTGAAGATTTTTGCAATGCCCATGCAGGATATCAAGATGATCCTGAAAATGGTVMHLSQSPSVSQLSVLSLSGVMLTDVGCAGCTGGACTCTATTGAAGATTTGGAAGTGACTTGTACCTGGAAGCTACCCACCTTGGCGAAATTTSPEPLQALLERASATLQDLVFDECGITCTCCTTACCTGGGCCAGATGATTAATCTGCGTAGACTCCTCCTCTCCCACATCCATGCATCTTCCTTDDQLLALLPSLSHCSQLTTLSFYGNACATTTCCCCGGAGAAGGAAGAGCAGTATATCGCCCAGTTCACCTCTCAGTTCCTCAGTCTGCAGTGSISISALQSLLQHLIGLSNLTHVLYPCCTGCAGGCTCTCTATGTGGACTCTTTATTTTTCCTTAGAGGCCGCCTGGATCAGTTGCTCAGGCACVPLESYEDIHGTLHLERLAYLHARLRGTGATGAACCCCTTGGAAACCCTCTCAATAACTAACTGCCGGCTTTCGGAAGGGGATGTGATGCATCELLCELGRPSMVWLSANPCPHCGDRTTGTCCCAGAGTCCCAGCGTCAGTCAGCTAAGTGTCCTGAGTCTAAGTGGGGTCATGCTGACCGATGTFYDPEPILCPCFMPNAAGTCCCGAGCCCCTCCAAGCTCTGCTGGAGAGAGCCTCTGCCACCCTCCAGGACCTGGTCTTTGATGAGTGTGGGATCACGGATGATCAGCTCCTTGCCCTCCTGCCTTCCCTGAGCCACTGCTCCCAGCTTACAACCTTAAGCTTCTACGGGAATTCCATCTCCATATCTGCCTTGCAGAGTCTCCTGCAGCACCTCATCGGGCTGAGCAATCTGACCCACGTGCTGTATCCTGTCCCCCTGGAGAGTTATGAGGACATCCATGGTACCCTCCACCTGGAGAGGCTTGCCTATCTGCATGCCAGGCTCAGGGAGTTGCTGTGTGAGTTGGGGCGGCCCAGCATGGTCTGGCTTAGTGCCAACCCCTGTCCTCACTGTGGGGACAGAACCTTCTATGACCCGGAGCCCATCCTGTGCCCCTGTTTCATGCCTAACTAGCTGGGTGCACATATCAAATGCTTCATTCTGCATACTTGGACACTAAAGCCAGGATGTGCATGCATCTTGAAGCAACAAAGCAGCCACAGTTTCAGACAAATGTTCAGTGTGAGTGAGGAAAACATGTTCAGTGAGGAAAAAACATTCAGACAAATGTTCAGTGAGGAAAAAAAGGGGAAGTTGGGGATAGGCAGATGTTGACTTGAGGAGTTAATGTGATCTTTGGGGAGATACATCTTATAGAGTTAGAAATAGAATCTGAATTTCTAAAGGGAGATTCTGGCTTGGGAAGTACATGTAGGAGTTAATCCCTGTGTAGACTGTTGTAAAGAAACTGTTGAAAATAAAGAGAAGCAATGTGAAGCAAAAAAAAAAAAAAAAAA SEQ.ID NO. 13 SEQ.ID NO. 63CGGCTGAGAGGCAGCGAACTCATCTTTGCCAGTACAGGAGCTTGTGCCGTGGCCCACAGCCCACAGCMGWDLTVKMLAGNEFQVSLSSSMSVSCCACAGCCATGGGCTGGGACCTGACGGTGAAGATGCTGGCGGGCAACGAATTCCAGGTGTCCCTGAGELKAQITQKIGVHAFQQRLAVHPSGVCAGCTCCATGTCGGTGTCAGAGCTGAAGGCGCAGATCACCCAGAAGATTGGCGTGCACGCCTTCCAGALQDRVPLASQGLGPGSTVLLVVDKCCAGCGTCTGGCTGTCCACCCGAGCGGTGTGGCGCTGCAGGACAGGGTCCCCCTTGCCAGCCAGGGCCDEPLSILVRNNKGRSSTYEVRLTQTVTGGGCCCTGGCAGCACGGTCCTGCTGGTGGTGGACAAATGCGACGAACCTCTGAGCATCCTGGTGAGAHLKQQVSGLEGVQDDLFWLTFEGKPGAATAACAAGGGCCGCAGCAGCACCTACGAGGTCCGGCTGACGCAGACCGTGGCCCACCTGAAGCAGLEDQLPLGEYGLKPLSTVFMNLRLRGCAAGTGAGCGGGCTGGAGGGTGTGCAGGACGACCTGTTCTGGCTGACCTTCGAGGGGAAGCCCCTGGGGTEPGGRSAGGACCAGCTCCCGCTGGGGGAGTACGGCCTCAAGCCCCTGAGCACCGTGTTCATGAATCTGCGCCTGCGGGGAGGCGGCACAGAGCCTGGCGGGCGGAGCTAAGGGCCTCCACCAGCATCCGAGCAGGATCAAGGGCCGGAAATAAAGGCTGTTGTAAGAGAAT SEQ.ID NO. 14 STAR clone:TGCCCACTTGGCCCCTCCTTCCAAGGTGTACTTTACTTCCTTTCATTCCTGCTCTAATACTGTTTAGTACATTTTCACTCCTGCTCTAAAACTTGCCTCAGTCTCTCACTGTGCCTTATGCCCCTCAGCTGAATTCTTTCTTCTGAGCAGGCAGGAATTGAGGTTGCTGCAGACGTGTATGCATTTGCCACCAGTAACATACTTTGGTGCCACATGACTAGGATATGTTCTCTAGTGCTAACATGTTCGTTTACAGTTCTTAGGACTCCCTGATA SEQ.ID NO. 15 SEQ.ID NO. 64GGCCGCCTGCGCGCCGCCAACAGCCTAGCGCTGCGCCGCGTGGCCGCCGCCTTCTCGCTGGCCCCGCMRWVRHDAPARRGQLRRLLEHVRLPLTGGCCGAGCGCTGCGGCCGCGTCCTGCGTCAGGCCTTCGCCGAGGTGGCGCGCCACGCCGACTTCCTLAPAYFLEKVEADELLQACGECRPLLGGAGCTGGCGCCTGACGAGGTGGTGGCGCTGCTGGCGGACCCCGCGCTGGGCGTGGCGCGCGAGGAGLEARACFILGREAGALRTRPRRFMDLGCCGTGTTTGAAGCGGCCATGCGCTGGGTGCGCCACGACGCGCCGGCCCGCCGCGGCCAGCTGCGACAEVIVVIGGCDRKGLLKLPFADAYHPGCCTGCTGGAGCACGTGCGCCTGCCGCTACTGGCGCCCGCTTACTTCCTGGAGAAGGTGGAGGCGGAESQRWTPLPSLPGYTRSEFAACALRNCGAGCTGCTGCAGGCCTGCGGCGAGTGCCGCCCGCTGCTGCTCGAGGCTCGCGCCTGCTTCATCCTGDVYVSGGHINSHDVWMFSSHLHTWIKGGCCGCGAGGCCGGTGCGCTGCGGACCCGGCCGCGGAGATTCATGGACCTAGCTGAAGTGATCGTGGVASLHKGRWRHKMAVVQGQLFAVGGFTCATCGGCGGTTGCGACCGCAAAGGTCTCCTGAAGCTGCCCTTCGCCGATGCCTACCATCCAGAGAGDGLRRLHSVERYDPFSNTWAAAAPLPCCAGCGGTGGACCCCACTGCCCAGCCTGCCCGGCTACACTCGCTCAGAATTCGCCGCCTGTGCTCTCEAVSSAAVASCAGKLFVIGGARQGGVCGCAATGACGTCTACGTCTCCGGAGGCCACATCAACAGTCATGATGTGTGGATGTTTAGCTCCCATCNTDKVQCFDPKEDRWSLRSPAPFSQRTGCACACCTGGATCAAGGTAGCCTCTCTGCACAAGGGCAGGTGGAGGCACAAGATGGCAGTTGTGCACLEAVSLEDTIYVMGGLMSKIFTYDPGGGGCAGCTGTTCGCGGTGGGTGGCTTCGACGGCCTGAGGCGCCTGCACAGCGTGGAGCGCTACGACGTDVWGEAAVLPSPVESCGVTVCDGKCCCTTCTCCAACACCTGGGCGGCCGCCGCGCCCCTCCCGGAGGCCGTGAGCTCGGCGGCGGTGGCGTVHILGGRDDRGESTDKVFTFDPSSGQCCTGCGCGGGCAAGCTCTTCGTGATTGGGGGCGCCAGGCAGGGCGGCGTCAACACGGACAAGGTGCAVEVQPSLQRCTSSHGCVTIIQSLGRGTGCTTTGACCCCAAGGAGGACCGGTGGAGCCTGCGGTCACCAGCACCCTTCTCACAGCGGTGTCTCGAGGCTGTCTCCCTTGAGGACACCATCTATGTCATGGGGGGTCTCATGAGCAAAATCTTCACCTATGATCCAGGCACAGATGTGTGGGGGGAGGCAGCTGTCCTCCCCAGCCCTGTGGAAAGCTGTGGAGTCACTGTGTGTGACGGGAAGGTCCACATCCTTGGCGGGCGGGATGATCGCGGAGAAAGCACCGATAAGGTCTTCACCTTTGACCCCAGCAGTGGGCAGGTGGAGGTCCAGCCATCCCTGCAGCGCTGCACCAGCTCCCACGGCTGTGTCACCATCATCCAGAGCTTGGGCAGGTGATTCAGATTTGGACAGCCTGAGCCAGGAGGCGGAGAGGCAGGCGGAGCTCAGATGCACACTCTGCTCCCTCATGGCACCTCCACGCAAACAGCCCTTAACTTAATGGTCCCTTTTCTTGTATAAATAAAATCTTGTTGGGTCTGTGTTCCAGCTGCAGTCTGCCCTGCCTGGAGATGGAATGTCTAAAAAAAAAAAAAAAA SEQ.ID NO. 16 STAR clone:TTTCTAGCAGCCTGGGCAATGGCGGGCGCCCCTCCCCCAGCCTCGCTGCTGCCTTGCAGTTTGATCTCAGACTGCTGTGCTAGCAATCAGCAAGACTCCGTGGGCGTAGGACCCTCCGAGCCAGGTTGCAAGAAAGCTCAAGTAGCCTATGGAGAGGATGCAAGGCTTCCAGCTGATGCCCTCAGCCAGGCTCAGTAGCAGCCAGAACTAGCCTACCAACGAACCTGCTGATCATGTGCATAAGCCACCTTGAACGTCGATCCTCCTGCCTGGTGGAGCCATCCCAGCTGATGCCACATGAAGCAGACACAAGCTGTCCCTACTAAGCTCTGCTCAAGTTGGATATTCATGAGTGAAATAAATGACTGTTACTAA SEQ.ID NO. 17 SEQ.ID NO. 65GAGTCACCAAGGAAGGCAGCGGCAGCTCCACTCAGCCAGTACCCAGATACGCTGGGAACCTTCCCCAMASLGQILFWSIISIIIILAGAIALIGCCATGGCTTCCCTGGGGCAGATCCTCTTCTGGAGCATAATTAGCATCATCATTATTCTGGCTGGAGIGFGISGRHSITVTTVASAGNIGEDGCAATTGCACTCATCATTGGCTTTGGTATTTCAGGGAGACACTCCATCACAGTCACTACTGTCGCCTCIQSCTFEPDIKLSDIVIQWLKEGVLGAGCTGGGAACATTGGGGAGGATGGAATCCAGAGCTGCACTTTTGAACCTGACATCAAACTTTCTGATLVHEFKEGKDELSEQDEMFRGRTAVFATCGTGATACAATGGCTGAAGGAAGGTGTTTTAGGCTTGGTCCATGAGTTCAAAGAAGGCAAAGATGADQVIVGNASLRLKNVQLTDAGTYKCAGCTGTCGGAGCAGGATGAAATGTTCAGAGGCCGGACAGCAGTGTTTGCTGATCAAGTGATAGTTGGYIITSKGKGNANLEYKTGAFSMPEVNCAATGCCTCTTTGCGGCTGAAAAACGTGCAACTCACAGATGCTGGCACCTACAAATGTTATATCATCVDYNASSETLRCEAPRWFPQPTVVWAACTTCTAAAGGCAAGGGGAATGCTAACCTTGAGTATAAAACTGGAGCCTTCAGCATGCCGGAAGTGASQVDQGANFSEVSNTSFELNSENVTMATGTGGACTATAATGCCAGCTCAGAGACCTTGCGGTGTGAGGCTCCCCGATGGTTCCCCCAGCCCACKVVSVLYNVTINNTYSCMIENDIAKAAGTGGTCTGGGCATCCCAAGTTGACCAGGGAGCCAACTTCTCGGAAGTCTCCAATACCAGCTTTGAGTGDIKVTESEIKRRSHLQLLNSKASLCTGAACTCTGAGAATGTGACCATGAAGGTTGTGTCTGTGCTCTACAATGTTACGATCAACAACACATCVSSFFAISWALLPLSPYLMLKACTCCTGTATGATTGAAAATGACATTGCCAAAGCAACAGGGGATATCAAAGTGACAGAATCGGAGATCAAAAGGCGGAGTCACCTACAGCTGCTAAACTCAAAGGCTTCTCTGTGTGTCTCTTCTTTCTTTGCCATCAGCTGGGCACTTCTGCCTCTCAGCCCTTACCTGATGCTAAAATAATGTGCCTCGGCCACAAAAAAGCATGCAAAGTCATTGTTACAACAGGGATCTACAGAACTATTTCACCACCAGATATGACCTAGTTTTATATTTCTGGGAGGAAATGAATTCATATCTAGAAGTCTGGAGTGAGCAAACAAGAGCAAGAAACAAAAAGAAGCCAAAAGCAGAAGGCTCCAATATGAACAAGATAAATCTATCTTCAAAGACATATTAGAAGTTGGGAAAATAATTCATGTGAACTAGAGTCAACTGTGTCAGGGCTAAGAAACCCTGGTTTTGAGTAGAAAAGGGCCTGGAAAGAGGGGAGCCAACAAATCTGTCTGCTTCCTCACATTAGTCATTGGCAAATAAGCATTCTGTCTCTTTGGCTGCTGCCTCAGCACAGAGAGCCAGAACTCTATCGGGCACCAGGATAACATCTCTCAGTGAACAGAGTTGACAAGGCCTATGGGAAATGCCTGATGGGATTATCTTCAGCTTGTTGAGCTTCTAAGTTTCTTTCCCTTCATTCTACCCTGCAAGCCAAGTTCTGTAAGAGAAATGCCTGAGTTCTAGCTCAGGTTTTCTTACTCTGAATTTAGATCTCCAGACCCTGCCTGGCCACAATTCAAATTAAGGCAACAAACATATACCTTCCATGAAGCACACACAGACTTTTGAAAGCAAGGACAATGACTGCTTGAATTGAGGCCTTGAGGAATGAAGCTTTGAAGGAAAAGAATACTTTGTTTCCAGCCCCCTTCCCACACTCTTCATGTGTTAACCACTGCCTTCCTGGACCTTGGAGCCACGGTGACTGTATTACATGTTGTTATAGAAAACTGATTTTAGAGTTCTGATCGTTCAAGAGAATGATTAAATATACATTTCCTAAAAAAAAAAAAAAA AASEQ.ID NO. 18 SEQ.ID NO. 66TCTTCGGACCTAGGCTGCCCTGCCGTCATGTCGCAAGGGATCCTTTCTCCGCCAGCGGGCTTGCTGTMSQGILSPPAGLLSDDDVVVSPMFESCCGATGACGATGTCGTAGTTTCTCCCATGTTTGAGTCCACAGCTGCAGATTTGGGGTCTGTGGTACGTAADLGSVVRKNLLSDCSVVSTSLEDCAAGAACCTGCTATCAGACTGCTCTGTCGTCTCTACCTCCCTAGAGGACAAGCAGCAGGTTCCATCTKQQVPSEDSMEKVKVYLRVRPLLPSEGAGGACAGTATGGAGAAGGTGAAAGTATACTTGAGGGTTAGGCCCTTGTTACCTTCAGAGTTGGAACLERQEDQGCVRIENVETLVLQAPKDSGACAGGAAGATCAGGGTTGTGTCCGTATTGAGAATGTGGAGACCCTTGTTCTACAAGCACCCAAGGAFALKSNERGIGQATHRFTFSQIFGPECTCGTTTGCCCTGAAGAGCAATGAACGGGGAATTGGCCAAGCCACACACAGGTTCACCTTTTCCCAGVGQASFFNLTVKEMVKDVLKGQNWLIATCTTTGGGCCAGAAGTGGGACAGGCATCCTTCTTCAACCTAACTGTGAAGGAGATGGTAAAGGATGYTYGVTNSGKTHTIQGTIKDGGILPRTACTCAAAGGGCAGAACTGGCTCATCTATACATATGGAGTCACTAACTCAGGGAAAACCCACACGATSLALIFNSLQGQLHPTPDLKPLLSNETCAAGGTACCATCAAGGATGGAGGGATTCTCCCCCGGTCCCTGGCGCTGATCTTCAATAGCCTCCAAVIWLDSKQIRQEEMKKLSLLNGGLQEGGCCAACTTCATCCAACACCTGATCTGAAGCCCTTGCTCTCCAATGAGGTAATCTGGCTAGACAGCAEELSTSLKRSVYIESRIGTSTSFDSGAGCAGATCCGACAGGAGGAAATGAAGAAGCTGTCCCTGCTAAATGGAGGCCTCCAAGAGGAGGAGCTIAGLSSISQCTSSSQLDETSHRWAQPGTCCACTTCCTTGAAGAGGAGTGTCTACATCGAAAGTCGGATAGGTACCAGCACCAGCTTCGACAGTDTAPLPVPANIRFSIWISFFEIYNELGGCATTGCTGGGCTCTCTTCTATCAGTCAGTGTACCAGCAGTAGCCAGCTGGATGAAACAAGTCATCLYDLLEPPSQQRKRQTLRLCEDQNGNGATGGGCACAGCCAGACACTGCCCCACTACCTGTCCCGGCAAACATTCGCTTCTCCATCTGGATCTCPYVKDLNWIHVQDAEEAWKLLKVGRKATTCTTTGAGATCTACAACGAACTGCTTTATGACCTATTAGAACCGCCTAGCCAACAGCGCAAGAGGNQSFASTHLNQNSSRSHSIFSIRILHCAGACTTTGCGGCTATGCGAGGATCAAAATGGCAATCCCTATGTGAAAGATCTCAACTGGATTCATGLQGEGDIVPKISELSLCDLAGSERCKTGCAAGATGCTGAGGAGGCCTGGAAGCTCCTAAAAGTGGGTCGTAAGAACCAGAGCTTTGCCAGCACDQKSGERLKEAGNINTSLHTLGRCIACCACCTCAACCAGAACTCCAGCCGCAGTCACAGCATCTTCTCAATCAGGATCCTACACCTTCAGGGGALRQNQQNRSKQNLVPFRDSKLTRVFGAAGGAGATATAGTCCCCAAGATCAGCGAGCTGTCACTCTGTGATCTGGCTGGCTCAGAGCGCTGCAQGFFTGRGRSCMIVNVNPCASTYDETAAGATCAGAAGAGTGGTGAACGGTTGAAGGAAGCAGGAAACATTAACACCTCTCTACACACCCTGGGLHVAKFSAIASQLVHAPPMQLGFPSLCCGCTGTATTGCTGCCCTTCGTCAAAACCAGCAGAACCGGTCAAAGCAGAACCTGGTTCCCTTCCGTHSFIKEHSLQVSPSLEKGAKADTGLDGACAGCAAGTTGACTCGAGTGTTCCAAGGTTTCTTCACAGGCCGAGGCCGTTCCTGCATGATTGTCADDIENEADISMYGKEELLQVVEAMKTATGTGAATCCCTGTGCATCTACCTATGATGAAACTCTTCATGTGGCCAAGTTCTCAGCCATTGCTAGLLLKERQEKLQLEMHLRDEICNEMVECCAGCTTGTGCATGCCCCACCTATGCAACTGGGATTCCCATCCCTGCACTCGTTCATCAAGGAACATQMQQREQWCSEHLDTQKELLEEMYEEAGTCTTCAGGTATCCCCCAGCTTAGAGAAAGGGGCTAAGGCAGACACAGGCCTTGATGATGATATTGKLNILKESLTSFYQEEIQERDEKIEEAAAATGAAGCTGACATCTCCATGTATGGCAAAGAGGAGCTCCTACAAGTTGTGGAAGCCATGAAGACLEALLQEARQQSVAHQQSGSELALRRACTGCTTTTGAAGGAACGACAGGAAAAGCTACAGCTGGAGATGCATCTCCGAGATGAAATTTGCAATSQRLAASASTQQLQEVKAKLQQCKAEGAGATGGTAGAACAGATGCAACAGCGGGAACAGTGGTGCAGTGAACATTTGGACACCCAAAAGGAACLNSTTEELHKYQKMLEPPPSAKPFTITATTGGAGGAAATGTATGAAGAAAAACTAAATATCCTCAAGGAGTCACTGACAAGTTTTTACCAAGADVDKKLEEGQKNIRLLRTELQKLGESAGAGATTCAGGAGCGGGATGAAAAGATTGAAGAGCTAGAAGCTCTCTTGCAGGAAGCCAGACAACAGLQSAERACCHSTGAGKLRQALTTCDDTCAGTGGCCCATCAGCAATCAGGGTCTGAATTGGCCCTACGGCGGTCACAAAGGTTGGCAGCTTCTGILIKQDQTLAELQNNMVLVKLDLRKKCCTCCACCCAGCAGCTTCAGGAGGTTAAAGCTAAATTACAGCAGTGCAAAGCAGAGCTAAACTCTACAACIAEQYHTVLKLQGQVSAKKRLGTCACTGAAGAGTTGCATAAGTATCAGAAAATGTTAGAACCACCACCCTCAGCCAAGCCCTTCACCATTNQENQQPNQQPPGKKPFLRNLLPRTPGATGTGGACAAGAAGTTAGAAGAGGGCCAGAAGAATATAAGGCTGTTGCGGACAGAGCTTCAGAAACTCQSSTDCSPYARILRSRRSPLLKSGTTGGTGAGTCTCTCCAATCAGCAGAGAGAGCTTGTTGCCACAGCACTGGGGCAGGAAAACTTCGTCAPFGKKYAGCCTTGACCACTTGTGATGACATCTTAATCAAACAGGACCAGACTCTGGCTGAACTGCAGAACAACATGGTGCTAGTGAAACTGGACCTTCGGAAGAAGGCAGCATGTATTGCTGAGCAGTATCATACTGTGTTGAAACTCCAAGGCCAGGTTTCTGCCAAAAAGCGCCTTGGTACCAACCAGGAAAATCAGCAACCAAACCAACAACCACCAGGGAAGAAACCATTCCTTCGAAATTTACTTCCCCGAACACCAACCTGCCAAAGCTCAACAGACTGCAGCCCTTATGCCCGGATCCTACGCTCACGGCGTTCCCCTTTACTCAAATCTGGGCCTTTTGGCAAAAAGTACTAAGGCTGTGGGGAAAGAGAAGAGCAGTCATGGCCCTGAGGTGGGTCAGCTACTCTCCTGAAGAAATAGGTCTCTTTTATGCTTTACCATATATCAGGAATTATATCCAGGATGCAATACTCAGACACTAGCTTTTTTCTCACTTTTGTATTATAACCACCTATGTAATCTCATGTTGTTGTTTTTTTTTATTTACTTATATGATTTCTATGCACACAAAAACAGTTATATTAAAGATATTATTGTTCACATTTTTTATTGAAAAAAAAAAAAAA STAR clone (SEQ.ID NO. 19):SEQ.ID NO.  67TCCTTGTTACGATGAAGAAACTAAATCTCAGGAAGAAAAAACTAAGTGAAGACNAAAGAAGGATTTGMFIWTSGRTSSSYRHDEKRNIYQKIRAACTGAGGTTTGTCAGACTCTCGGGACCATGCTGTTGAAACCACTAAACCACGCTGCCTCTGGGTCADHDLLDKRKTVTALKAGEDRAILLGLCTTGGTAAACAGCATTTAACCATTAAGAAAGTCATTAATAAAATTCCTTGTGCTCTCCTTGAGATTAAMMVCSIMMYFLLGITLLRSYMQSVW CAAGCCATTGATTTGCCAATEESQCTLLNASITETFNCSFSCGPD NM_005832: CWKLSQYPCLQVYVNLTSSGEKLLLYGCTGGGCACCGTTCTGTTTTCTTTCTTTTCTTAATCCTATCCAAGTATGCAGTACGCTCTTGGGTCGHTEETIKINQTCTCATGAGACCCAGGGGCATGTTGGAAAGAACTGAGAGAAAGAGCAACAAAGCGGCGAGTGGTGTGKCSYIPKCGKNFEESMSLVNVVMENFAGAGGGCAGCACGCGCTGTGGGGCCCTTCCAGAGAAATGTACTGAAAAAGTCTACGCAATGTCTGGGRKYQHFSCYSDPEGNQKSVILTKLYSATTTGCTAAACAATACCTGGAAAGCAGACAGGTCTTTTTGCCATTCCTCCAGGACATCCACCATAAGSNVLEHSLFWPTCMMAGGVAIVAMVKGAAAGGAGACCCTGGACCAACATTCTCTAAGATGTTTATATGGACCAGTGGCCGGACCTCTTCATCTLTQYLSLLCERIQRINRTATAGACATGATGAAAAAAGAAATATTTACCAGAAAATCAGGGACCATGACCTCCTGGACAAAAGGAAAACAGTCACAGCACTGAAGGCAGGAGAGGACCGAGCTATTCTCCTGGGACTGGCTATGATGGTGTGCTCCATCATGATGTATTTTCTGCTGGGAATCACACTCCTGCGCTCATACATGCAGAGCGTGTGGACCGAAGAGTCTCAATGCACCTTGCTGAATGCGTCCATCACGGAAACATTTAATTGCTCCTTCAGCTGTGGTCCAGACTGCTGGAAACTTTCTCAGTACCCCTGCCTCCAGGTGTACGTTAACCTGACTTCTTCCGGGGAAAAGCTCCTCCTCTACCACACAGAAGAGACAATAAAAATCAATCAGAAGTGCTCCTATATACCTAAATGTGGAAAAAATTTTGAAGAATCCATGTCCCTGGTGAATGTTGTCATGGAAAACTTCAGGAAGTATCAACACTTCTCCTGCTATTCTGACCCAGAAGGAAACCAGAAGAGTGTTATCCTAACAAAACTCTACAGTTCCAACGTGCTGTTCCATTCACTCTTCTGGCCAACCTGTATGATGGCTGGGGGTGTGGCAATTGTTGCCATGGTGAAACTTACACAGTACCTCTCCCTACTATGTGAGAGGATCCAACGGATCAATAGATAAATGCAAAAATGGATAAAATAATTTTTGTTAAAGCTCAAATACTGTTTTCTTTCATTCTTCACCAAAGAACCTTAAGTTTGTAACGTGCAGTCTGTTATGAGTTCCCTAATATATTCTTATATGTAGAGCAATAATGCAAAAGCTGTTCTATATGCAAACATGATGTCTTTATTATTCAGGAGAATAAATAACTGTTTTGTGTTGGTTGGTGGTTTTCATAATCTTATTTCTGTACTGGAACTAGTACTTTCTTCTCTCATTCCGCCAAAACAGGGCTCAGTTATTCATTTGCCAAGCTTCGTGGAGGAATGTAGGTGACATCAATGTGATAAAGTCTGTGTTCTGAGTTGTCAGATCTCTTGAAGACAATATTTTTCATCACTTATTGTTTACTAAAGCTACAGCCAAAAATATTTTTTTTTCTTATTCTAAACTGAGCCCTATAGCAAGTGAAGGGACCAGATTTCCTAATTAAAGGAAGTTAGGTACTTTTCTTGTATTTTTTACCATATCACTGTAAAGAAGAGGGGAAACCCAGCCAGCTACTTTTTTTCATCACTTTTTATTCATAACTTCAGATTTGTAAAACTAATTTCCAAAATATAAGCTGTTTTCATTAGCCAGTTCTATAATATCTTCCTGTGATTTATGTAGAAAATGAACACACCCCTTTTCCATTTAAGACCCTGCTACTGTGTGAAGAGATGATACTTACAAGGAGTGTCATTACCTGTGAGCTGACTGAATGTTGGTAGGTGCTCCATTACAATCCAGGAAAGTCTGTGTTACTGATATTTGTGTGGAAATCTTTATTTCACTTCAATTTAACCATTAGATGGTAAAATTAAGATGCTACTTGTTGGTAAAAATTGGTGGACTGGTTTCAATGGGTAAATGTGTTGTGGCAAATTAATGTGTTGGAATATTGCTCTTTGTGAATTTGTGCTTAAGTCAATGAATGTGTAGTATCTCCTTCTGACAAGCATTCCCTATTGGGATTTTAAAGCTATGTGCACAGAATATTAGTCTCTTCTACATGTTTTATTTTTCTATTTATAATTCCCTTTTTTGTTGTTATATTTTATACACAGAATAGATCTTTTTTCTAACACATATTTGAACTGAATAACAGACTTAAAGAAAGCCTTTGTTCACATTGCTATTTACTTTTGTGTTTGGGGGAAAATACGAGGGATTGATTTTAAATAAAAAACATTCCATCTTTCATTTAATATCAATATCAAAAGAAGAAGACAAACATCTATCTTTCTCATCTATATTTAAGTACCTTTTTGTAATGTAGTATCAAAGTTTTTTAGGTAATGCAAAATTTTACAAATCATTTGTGGAATGAATGGTAAAACTAATCTGATGAAATGGAAAATTATTCTGCAATATTGTAATTCATAGTTTGACTTTTCATAAGCAAATAAATCCCTAGGATGTAATCAGGACTTCAAATGTGTAATTAAATTTTTTTAAAAAAAATCTA SEQ.ID NO. 20STAR clone:GAACACAGCTAAGCAGATGGCTTGGGTCATCAGGACGTCCATTACATCCAAAGGAAGACAGCCTGTGACGTTTCAAAAGCAAAAGTCCCCTACCAGCCAGTGAAGCTACCTGATTTCTCAGTATCTTACGCCCAGTGACACGATCTACCCTCAAAACTTA SEQ.ID NO. 21 SEQ.ID NO. 68GAGACATTCCTCAATTGCTTAGACATATTCTGAGCCTACAGCAGAGGAACCTCCAGTCTCAGCACCAMNQTAILICCLIFLTLSGIQGVPLSRTGAATCAAACTGCGATTCTGATTTGCTGCCTTATCTTTCTGACTCTAAGTGGCATTCAAGGAGTACCTVRCTCISISNQPVNPRSLEKLEIIPTCTCTCTAGAACCGTACGCTGTACCTGCATCAGCATTAGTAATCAACCTGTTAATCCAAGGTCTTTAASQFCPRVEIIATMKKKGEKRCLNPEGAAAAACTTGAAATTATTCCTGCAAGCCAATTTTGTCCACGTGTTGAGATCATTGCTACAATGAAAASKAIKNLLKAVSKEMSKRSPAGAAGGGTGAGAAGAGATGTCTGAATCCAGAATCGAAGGCCATCAAGAATTTACTGAAAGCAGTTAGCAAGGAAATGTCTAAAAGATCTCCTTAAAACCAGAGGGGAGCAAAATCGATGCAGTGCTTCCAAGGATGGACCACACAGAGGCTGCCTCTCCCATCACTTCCCTACATGGAGTATATGTCAAGCCATAATTGTTCTTAGTTTGCAGTTACACTAAAAGGTGACCAATGATGGTCACCAAATCAGCTGCTACTACTCCTGTAGGAAGGTTAATGTTCATCATCCTAAGCTATTCAGTAATAACTCTACCCTGGCACTATAATGTAAGCTCTACTGAGGTGCTATGTTCTTAGTGGATGTTCTGACCCTGCTTCAAATATTTCCCTCACCTTTCCCATCTTCCAAGGGTACTAAGGAATCTTTCTGCTTTGGGGTTTATCAGAATTCTCAGAATCTCAAATAACTAAAAGGTATGCAATCAAATCTGCTTTTTAAAGAATGCTCTTTACTTCATGGACTTCCACTGCCATCCTCCCAAGGGGCCCAAATTCTTTCAGTGGCTACCTACATACAATTCCAAACACATACAGGAAGGTAGAAATATCTGAAAATGTATGTGTAAGTATTCTTATTTAATGAAAGACTGTACAAAGTATAAGTCTTAGATGTATATATTTCCTATATTGTTTTCAGTGTACATGGAATAACATGTAATTAAGTACTATGTATCAATGAGTAACAGGAAAATTTTAAAAATACAGATAGATATATGCTCTGCATGTTACATAAGATAAATGTGCTGAATGGTTTTCAAATAAAAATGAGGTACTCTCCTGGAAATATTAAGAAAGACTATCTAAATGTTGAAAGATCAAAAGGTTAATAAAGTAATTATAACT SEQ.ID NO. 22 STAR clone:TTTGCAGGTTTGATCTCAGACTGCTGTGCTAGTAATCAGCGAGATTCCGTGGGCGTAGGAGCCTCCAAGCCAGGTCCTGAAGAAAATGAAGTTGATGTTTCAGTGAGACACCTGTATGCCAGAGAGTAAAAGGGATTATTGTGGATTCCTGAGAATTTTCTACATATGAAATCATGTCATCTATGAACAGAGATGGGACTGTCTCGTTGGAGGAAAACAAGCTCAGGGCTCCCACTGATTCCACATTATGTTGCAAGCTCCTACGAAGCTCCCACTCA SEQ.ID NO. 23 SEQ.ID NO. 69TTTCTCCGCATGCGCGGGATCCCGGATGTGGATCAAGTTGGTGGGAAGCGTGCGGTGCCGCAGCAATMAALTIATGTGNWFSALALGVTLLKCGGCGGCGCTCACAATTGCCACGGGTACTGGCAATTGGTTTTCGGCTTTGGCGCTCGGGGTGACTCTTLLIPTYHSTDFEVHRNWLAITHSLPICTCAAATGCCTTCTCATCCCCACATACCATTCCACAGATTTTGAAGTACACCGAAACTGGCTTGCTASQWYYEATSEWTLDYPPFFAWFEYILTCACTCACAGTTTGCCAATATCACAGTGGTATTATGAGGCAACTTCAGAGTGGACGTTGGATTACCCSHVAKYFDQEMLNVHNLNYSSSRTLLCCCTTTCTTTGCATGGTTTGAGTATATCCTGTCACATGTTGCCAAATATTTTGATCAAGAAATGCTGFQRFSVIFMDVLFVYAVRECCKCIDGAATGTCCATAATTTGAATTACTCCAGCTCAAGGACCTTACTTTTCCAGAGATTTTCCGTCATCTTTAKKVGKELTEKPKFILSVLLLWNFGLLTGGATGTACTCTTTGTGTATGCTGTCCGTGAGTGCTGTAAATGCATTGATGGAAAAAAAGTGGGTAAIVDHIHFQYNGFLFGLMLLSIARLFQAGAACTTACAGAAAAGCCAAAATTTATTCTGTCGGTATTACTTCTGTGGAACTTCGGGTTATTAATTKRHMEGAFLFAVLLHFKHIYLYVAPAGTGGACCATATTCATTTTCAGTACAATGGCTTTTTATTTGGATTAATGCTACTCTCCATTGCACGATYGVYLLRSYCFTANKPDGSIRWKSFSTATTTCAGAAAAGGCATATGGAAGGAGCATTTCTCTTTGCTGTTCTCCTACATTTCAAGCATATCTAFVRVISLGLVVFLVSALSLGPFLALNCCTCTATGTAGCACCAGCTTATGGTGTATATCTGCTGCGATCCTACTGTTTCACTGCAAATAAACCAQLPQVFSRLFPFKRGLCHAYWAPNFWGATGGGTCTATTCGATGGAAGAGTTTCAGCTTTGTTCGTGTTATTTCCCTGGGACTGGTTGTTTTCTALYNALDKVLSVIGLKLKFLDPNNIPTAGTTTCTGCTCTTTCATTGGGTCCTTTCCTGGCCTTGAATCAGCTGCCTCAAGTCTTTTCCCGACTKASMTSGLVQQFQHTVLPSVTPLATLCTTTCCTTTCAAGAGGGGCCTCTGTCATGCATATTGGGCTCCAAACTTCTGGGCTTTGTACAATGCTICTLIAILPSIFCLWFKPQGPRGFLRTTGGACAAAGTGCTGTCTGTCATCGGTTTGAAATTGAAATTTCTTGATCCCAACAATATTCCCAAGGCLTLCALSSFMFGWHVHEKAILLAILCCTCAATGACAAGTGGTTTGGTTCAGCAGTTCCAACACACAGTCCTTCCCTCAGTGACTCCCTTGGCPMSLLSVGKAGDASIFLILTTTGHYSAACCCTCATCTGCACACTGATTGCCATATTGCCCTCTATTTTCTGTCTTTGGTTTAAACCCCAAGGGLFPLLFTAPELPIKILLMLLFTIYSICCCAGAGGCTTTCTCCGATGTCTAACTCTTTGTGCCTTGAGCTCCTTTATGTTTGGGTGGCATGTTCSSLKTLFRRSFTLVAQAGVQWHDLSATGAAAAAGCCATACTTCTAGCAATTCTCCCAATGAGCCTTTTGTCTGTGGGAAAAGCAGGAGACGCTTCGATTTTTCTGATTCTGACCACAACAGGACATTATTCCCTCTTTCCTCTGCTCTTCACTGCACCAGAACTTCCCATTAAAATCTTACTCATGTTACTATTCACCATATATAGTATTTCGTCACTGAAGACTTTATTCAGACGGAGTTTCACCCTTGTTGCCCAGGCTGGAGTGCAATGGCACGATCTCAGCTAACTGAAACCTCCGCCTCCCAGAAAAGAAAAACCTCTTTTTAATTGGATGGAAACTTTCTACCTGCTTGGCCTGGGGCCTCTGGAAGTCTGCTGTGAATTTGTATTCCCTTTCACCTCCTGGAAGGTGAAGTACCCCTTCATCCCTTTGTTACTAACCTCAGTGTATTGTGCAGTAGGCATCACATATGCTTGGTTCAAACTGTATGTTTCAGTATTGATTGACTCTGCTATTGGCAAGACAAAGAAACAATGAATAAAGGAACTGCTTAGATAT GSEQ.ID NO. 24 SEQ.ID NO. 70CATTATGCTAACAGCATAAACATGCAGGGGGTGGGAGCAGGGTCACAAAAGTGAGTGTTGTCAATTCMDDDAAPRVEGVPVAVHKHALHDGLRTACTTGGAATGAAAGGTTGAAATAATTTAAACAGTACGGGAAATGCAGAGCAATTTTCTCCTCTGGTQVAGPGAAAAHLPRWPPPQLAASRREGACAATATAGTGTCCAACACTTGGAAGTGATTTTTAAGAATGTTTATTTAAATTAAAAGGATGGATTAPPLSQRPHRTQGAGSPPETNEKLTNTCCAAGGAAAAAAAATAAGGAAAAGGAAAGAAAAAACTGAACAGAAAACGCAAAAGTATCAGTTTGGPQVKEKTCACTAACCTTTGCAAGGATACCTTTTTATTTTCTTTAAGATTCCTGTTGTTTATACACAGATTTTAAGTTTACTCCTACTGCTGACCCAAGTGAAATTCCTTCTCCAGTCACAGTGTCAACCTCTACCCCCCAACTGCAACGAGAGTTTTGAGGGGCATCAATCACACCGAGAAGTCACAGCCCCTCAACCACTGAGGTGTGGGGGGGTAGGGATCTGCATTTCTTCATATCAACCCCACACTATAGGGCACCTAAATGGGTGGGCGGTGGGGGAGACCGACTCACTTGAGTTTCTTGAAGGCTTCCTGGCCTCCAGCCACGTAATTGCCCCCGCTCTGGATCTGGTCTAGCTTCCGGATTCGGTGGCCAGTCCGCGGGGTGTAGATGTTCCTGACGGCCCCAAAGGGTGCCTGAACGCCGCCGGTCACCTCCTTCAGGAAGACTTCGAAGCTGGACACCTTCTTCTCATGGATGACGACGCGGCGCCCCGCGTAGAAGGGGTCCCCGTTGCGGTACACAAGCACGCTCTTCACGACGGGCTGAGACAGGTGGCTGGACCTGGCGCTGCTGCCGCTCATCTTCCCCGCTGGCCGCCGCCTCAGCTCGCTGCTTCGCGTCGGGAGGCACCTCCGCTGTCCCAGCGGCCTCACCGCACCCAGGGCGCGGGATCGCCTCCTGAAACGAACGAGAAACTGACGAATCCACAGGTGAAAGAGAAGTAACGGCCGTGCGCCTAGGCGTCCACCCAGAGGAGACACTAGGAGCTTGCAGGACTCGGAGTAGACGCTCAAGTTTTTCACCGTGGCGTGCACAGCCAATCAGGACCCGCAGTGCGCGCACCACACCAGGTTCACCTGCTACGGGCAGAATCAAGGTGGACAGCTTCTGAGCAGGAGCCGGAAACGCGCGGGGCCTTCAAACAGGCACGCCTAGTGAGGGCAGGAGAGAGGAGGACGCACACACACACACACACACAAATATGGTGAAACCCAATTTCTTACATCATATCTGTGCTACCCTTTCCAAACAGCCTAATTTTTCTTTTCTCTCTTCTTGCACCTTTACCCCTCAATCTCCTGCTTCCTCCCAAATTAAAGCAATTAAGTTCCTGG SEQ.ID NO. 25 SEQ.ID NO. 71CTCCTCCGAGCACTCGCTCACGGCGTCCCCTTGCCTGGAAAGATACCGCGGTCCCTCCAGAGGATTTMEPAAGSSMEPSADWLATAAARGRVEGAGGGACAGGGTCGGAGGGGGCTCTTCCGCCAGCACCGGAGGAAGAAAGAGGAGGGGCTGGCTGGTCEVRALLEAGALPNAPNSYGRRPIQVMACCAGAGGGTGGGGCGGACCGCGTGCGCTCGGCGGCTGCGGAGAGGGGGAGAGCAGGCAGCGGGCGGMMGSARVAELLLLHGAEPNCADPATLCGGGGAGCAGCATGGAGCCGGCGGCGGGGAGCAGCATGGAGCCTTCGGCTGACTGGCTGGCCACGGCTRPVHDAAREGFLDTLVVLHRAGARLCGCGGCCCGGGGTCGGGTAGAGGAGGTGCGGGCGCTGCTGGAGGCGGGGGCGCTGCCCAACGCACCGDVRDAWGRLPVDLAEELGHRDVARYLAATAGTTACGGTCGGAGGCCGATCCAGGTCATGATGATGGGCAGCGCCCGAGTGGCGGAGCTGCTGCRAAAGGTRGSTGCTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCACTCTCACCCGACCCGTGCACGACGCTGCNHARIDAAEGPSDIPDCCGGGAGGGCTTCCTGGACACGCTGGTGGTGCTGCACCGGGCCGGGGCGCGGCTGGACGTGCGCGATGCCTGGGGCCGTCTGCCCGTGGACCTGGCTGAGGAGCTGGGCCATCGCGATGTCGCACGGTACCTGCGCGCGGCTGCGGGGGGCACCAGAGGCAGTAACCATGCCCGCATAGATGCCGCGGAAGGTCCCTCAGACATCCCCGATTGAAAGAACCAGAGAGGCTCTGAGAAACCTCGGGAAACTTAGATCATCAGTCACCGAAGGTCCTACAGGGCCACAACTGCCCCCGCCACAACCCACCCCGCTTTCGTAGTTTTCATTTAGAAAATAGAGCTTTTAAAAATGTCCTGCCTTTTAACGTAGATATATGCCTTCCCCCACTACCGTAAATGTCCATTTATATCATTTTTTATATATTCTTATAAAAATGTAAAAAAGAAAAACACCGCTTCTGCCTTTTCACTGTGTTGGAGTTTTCTGGAGTGAGCACTCACGCCCTAAGCGCACATTCATGTGGGCATTTCTTGCGAGCCTCGCAGCCTCCGGAAGCTGTCGACTTCATGACAAGCATTTTGTGAACTAGGGAAGCTCAGGGGGGTTACTGGCTTCTCTTGAGTCACACTGCTAGCAAATGGCAGAACCAAAGCTCAAATAAAAATAAAATAATTTTCATTCATTCACTCAAAA SEQ.ID NO. 26 SEQ.ID NO. 72AGTGGACTCACGCAGGCGCAGGAGACTACACTTCCCAGGAACTCCGGGCCGCGTTGTTCGCTGGTACMSQVKSSYSYDAPSDFINFSSLDDEGCTCCTTCTGACTTCCGGTATTGCTGCGGTCTGTAGGGCCAATCGGGAGCCTGGAATTGCTTTCCCGGDTQNIDSWFEEKANLENKLLGKNGTGCGCTCTGATTGGTGCATTCGACTAGGCTGCCTGGGTTCAAAATTTCAACGATACTGAATGAGTCCCGGLFQGKTPLRKANLQQAIVTPLKPVDCGGCGGGTTGGCTCGCGCTTCGTTGTCAGATCTGAGGCGAGGCTAGGTGAGCCGTGGGAAGAAAAGANTYYKEAEKENLVEQSIPSNACSSLEGGGAGCAGCTAGGGCGCGGGTCTCCCTCCTCCCGGAGTTTGGAACGGCTGAAGTTCACCTTCCAGCCVEAAISRKTPAQPQRRSLRLSAQKDLCCTAGCGCCGTTCGCGCCGCTAGGCCTGGCTTCTGAGGCGGTTGCGGTGCTCGGTCGCCGCCTAGGCEQKEKHHVKMKAKRCATPVIIDEILPGGGGCAGGGTGCGAGCAGGGGCTTCGGGCCACGCTTCTCTTGGCGACAGGATTTTGCTGTGAAGTCCSKKMKVSNNKKKPEEEGSAHQDTAEKGTCCGGGAAACGGAGGAAAAAAAGAGTTGCGGGAGGCTGTCGGCTAATAACGGTTCTTGATACATATNASSPEKAKGRHTVPCMPPAKQKFLKTTGCCAGACTTCAAGATTTCAGAAAAGGGGTGAAAGAGAAGATTGCAACTTTGAGTCAGACCTGTAGSTEEQELEKSMKMQQEVVEMRKKNEEGCCTGATAGACTGATTAAACCACAGAAGGTGACCTGCTGAGAAAAGTGGTACAAATACTGGGAAAAAFKKLALAGIGQPVKKSVSQVTKSVDFCCTGCTCTTCTGCGTTAAGTGGGAGACAATGTCACAAGTTAAAAGCTCTTATTCCTATGATGCCCCCHFRTDERIKQHPKNQEEYKEVNFTSETCGGATTTCATCAATTTTTCATCCTTGGATGATGAAGGAGATACTCAAAACATAGATTCATGGTTTGLRKHPSSPARVTKGCTIVKPFNLSQGAGGAGAAGGCCAATTTGGAGAATAAGTTACTGGGGAAGAATGGAACTGGAGGGCTTTTTCAGGGCAAKKRTFDETVSTYVPLAQQVEDFHKRTAACTCCTTTGAGAAAGGCTAATCTTCAGCAAGCTATTGTCACACCTTTGAAACCAGTTGACAACACTPNRYHLRSKKDDINLLPSKSSVTKICTACTACAAAGAGGCAGAAAAAGAAAATCTTGTGGAACAATCCATTCCGTCAAATGCTTGTTCTTCCCRDPQTPVLQTKHRARAVTCKSTAELETGGAAGTTGAGGCAGCCATATCAAGAAAAACTCCAGCCCAGCCTCAGAGAAGATCTCTTAGGCTTTCAEELEKLQQYKFKARELDPRILEGGPTGCTCAGAAGGATTTGGAACAGAAAGAAAAGCATCATGTAAAAATGAAAGCCAAGAGATGTGCCACTILPKKPPVKPPTEPIGFDLEIEKRIQCCTGTAATCATCGATGAAATTCTACCCTCTAAGAAAATGAAAGTTTCTAACAACAAAAAGAAGCCAGERESKKKTEDEHFEFHSRPCPTKILEAGGAAGAAGGCAGTGCTCATCAAGATACTGCTGAAAAGAATGCATCTTCCCCAGAGAAAGCCAAGGGDVVGVPEKKVLPITVPKSPAFALKNRTAGACATACTGTGCCTTGTATGCCACCTGCAAAGCAGAAGTTTCTAAAAAGTACTGAGGAGCAAGAGIRMPTKEDEEEDEPVVIKAQPVPHYGCTGGAGAAGAGTATGAAAATGCAGCAAGAGGTGGTGGAGATGCGGAAAAAGAATGAAGAATTCAAGAVPFKPQIPEARTVEICPFSFDSRDKEAACTTGCTCTGGCTGGAATAGGGCAACCTGTGAAGAAATCAGTGAGCCAGGTCACCAAATCAGTTGARQLQKEKKIKELQKGEVPKFKALPLPCTTCCACTTCCGCACAGATGAGCGAATCAAACAACATCCTAAGAACCAGGAGGAATATAAGGAAGTGHFDTINLPEKKVKNVTQIEPFCLETDAACTTTACATCTGAACTACGAAAGCATCCTTCATCTCCTGCCCGAGTGACTAAGGGATGTACCATTGRRGALKAQTWKHQLEEELRQQKEAACTTAAGCCTTTCAACCTGTCCCAAGGAAAGAAAAGAACATTTGATGAAACAGTTTCTACATATGTGCCFKARPNTVISQEPFVPKKEKKSVAEGCCTTGCACAGCAAGTTGAAGACTTCCATAAACGAACCCCTAACAGATATCATTTGAGGAGCAAGAAGLSGSLVQEPFQLATEKRAKERQELEKGATGATATTAACCTGTTACCCTCCAAATCTTCTGTGACCAAGATTTGCAGAGACCCACAGACTCCTGRMAEVEAQKAQQLEEARLQEEEQKKETACTGCAAACCAAACACCGTGCACGGGCTGTGACCTGCAAAAGTACAGCAGAGCTGGAGGCTGAGGAELARLRRELVHKANPIRKYQGLEIKSGCTCGAGAAATTGCAACAATACAAATTCAAAGCACGTGAACTTGATCCCAGAATACTTGAAGGTGGGSDQPLTVPVSPKFSTRFHCCCCATCTTGCCCAAGAAACCACCTGTGAAACCACCCACCGAGCCTATTGGCTTTGATTTGGAAATTGAGAAAAGAATCCAGGAGCGAGAATCAAAGAAGAAAACAGAGGATGAACACTTTGAATTTCATTCCAGACCTTGCCCTACTAAGATTTTGGAAGATGTTGTGGGTGTTCCTGAAAAGAAGGTACTTCCAATCACCGTCCCCAAGTCACCAGCCTTTGCATTGAAGAACAGAATTCGAATGCCCACCAAAGAAGATGAGGAAGAGGACGAACCGGTAGTGATAAAAGCTCAACCTGTGCCACATTATGGGGTGCCTTTTAAGCCCCAAATCCCAGAGGCAAGAACTGTGGAAATATGCCCTTTCTCGTTTGATTCTCGAGACAAAGAACGTCAGTTACAGAAGGAGAAGAAAATAAAAGAACTGCAGAAAGGGGAGGTGCCCAAGTTCAAGGCACTTCCCTTGCCTCATTTTGACACCATTAACCTGCCAGAGAAGAAGGTAAAGAATGTGACCCAGATTGAACCTTTCTGCTTGGAGACTGACAGAAGAGGTGCTCTGAAGGCACAGACTTGGAAGCACCAGCTGGAAGAAGAACTGAGACAGCAGAAAGAAGCAGCTTGTTTCAAGGCTCGTCCAAACACCGTCATCTCTCAGGAGCCCTTTGTTCCCAAGAAAGAGAAGAAATCAGTTGCTGAGGGCCTTTCTGGTTCTCTAGTTCAGGAACCTTTTCAGCTGGCTACTGAGAAGAGAGCCAAAGAGCGGCAGGAGCTGGAGAAGAGAATGGCTGAGGTAGAAGCCCAGAAAGCCCAGCAGTTGGAGGAGGCCAGACTACAGGAGGAAGAGCAGAAAAAAGAGGAGCTGGCCAGGCTACGGAGAGAACTGGTGCATAAGGCAAATCCAATACGCAAGTACCAGGGTCTGGAGATAAAGTCAAGTGACCAGCCTCTGACTGTGCCTGTATCTCCCAAATTCTCCACTCGATTCCACTGCTAAACTCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCTGCTCTTAACCTCAAACCTAGGACCGTCTTGCTTTGTCATTGGGCATGGAGAGAACCCATTTCTCCAGACTTTTACCTACCCGTGCCTGAGAAAGCATACTTGACAACTGTGGACTCCAGTTTTGTTGAGAATTGTTTTCTTACATTACTAAGGCTAATAATGAGATGTAACTCATGAATGTCTCGATTAGACTCCATGTAGTTACTTCCTTTAAACCATCAGCCGGCCTTTTATATGGGTCTTCACTCTGACTAGAATTTAGTCTCTGTGTCAGCACAGTGTAATCTCTATTGCTATTGCCCCTTACGACTCTCACCCTCTCCCCACTTTTTTTAAAAATTTTAACCAGAAAATAAAGATAGTTAAATCCTAAGATAGAGATTAAGTCATGGTTTAAATGAGGAACAATCAGTAAATCAGATTCTGTCCTCTTCTCTGCATACCGTGAATTTATAGTTAAGGATCCCTTTGCTGTGAGGGTAGAAAACCTCACCAACTGCACCAGTGAGGAAGAAGACTGCGTGGATTCATGGGGAGCCTCACAGCAGCCACGCAGCAGGCTCTGGGTGGGGCTGCCGTTAAGGCACGTTCTTTCCTTACTGGTGCTGATAACAACAGGGAACCGTGCAGTGTGCATTTTAAGACCTGGCCTGGAATAAATACGTTTTGTCTTTCCCTCAAAAAAAAAAAAAAAAAAAAAAASEQ.ID NO. 27 SEQ.ID NO. 73AAACGCGGGCGGGCGGGCCCGCAGTCCTGCAGTTGCAGTCGTGTTCTCCGAGTTCCTGTCTCTCTGCMASQNRDPAATSVAAARKGAEPSGGACAACGCCGCCCGGATGGCTTCCCAAAACCGCGACCCAGCCGCCACTAGCGTCGCCGCCGCCCGTAAAARGPVGKRLQQELMTLMMSGDKGISAGGAGCTGAGCCGAGCGGGGGCGCCGCCCGGGGTCCGGTGGGCAAAAGGCTACAGCAGGAGCTGATGAFPESDNLFKWVGTIHGAAGTVYEDLRCCCTCATGATGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATCAGACAACCTTTTCAAATGGGTYKLSLEFPSGYPYNAPTVKFLTPCYHAGGGACCATCCATGGAGCAGCTGGAACAGTATATGAAGACCTGAGGTATAAGCTCTCGCTAGAGTTCPNVDTQGNICLDILKEKWSALYDVRTCCCAGTGGCTACCCTTACAATGCGCCCACAGTGAAGTTCCTCACGCCCTGCTATCACCCCAACGTGGILLSIQSLLGEPNIDSPLNTHAAELWACACCCAGGGTAACATATGCCTGGACATCCTGAAGGAAAAGTGGTCTGCCCTGTATGATGTCAGGACKNPTAFKKYLQETYSKQVTSQEPCATTCTGCTCTCCATCCAGAGCCTTCTAGGAGAACCCAACATTGATAGTCCCTTGAACACACATGCTGCCGAGCTCTGGAAAAACCCCACAGCTTTTAAGAAGTACCTGCAAGAAACCTACTCAAAGCAGGTCACCAGCCAGGAGCCCTGACCCAGGCTGCCCAGCCTGTCCTTGTGTCGTCTTTTTAATTTTTCCTTAGATGGTCTGTCCTTTTTGTGATTTCTGTATAGGACTCTTTATCTTGAGCTGTGGTATTTTTGTTTTGTTTTTGTCTTTTAAATTAAGCCTCGGTTGAGCCCTTGTATATTAAATAAATGCATTTTTGTCCTTTTTTAGACAAAAAAAAAAAAAAA SEQ.ID NO. 28CAGCTAAATTTTAAAGGTGTTTTTGTAGAGATGAGGTTTCACTATATTGCCCAGGCTGGTCTCGAACTCCTGGACTTAAGTGATCCTTCCTCTTTGGCCTCCCAAAGTGCTGGGATTACAGGCATGAGCCACTGCCCCAGCCAAGACTGTCTTTTCTCCATTGTATTGCGTTTGCTTCCTTGTCAAAGATCAGTTGACTATATTTGTGTGGGGCTATTTCTGGGCTCCCTATTTGTTTCCAGTGATTATGTCTATTTTTTCACCATTACCACCCTATCTTAATTACTGTAGCTTTATAGTGAGTCTTAAAGTTGGGTAATATCAGTCTTCTGACCTTTTTCTCTTTCAATATTGTGCCAGCTATTCTGGGTCTTTTGCCTTTCCATGTAAACTTTAGAACCAGTTTGTCAGGATCCACAAAATACTTTGCTGGGTTTTGATTGGGATTGCATTGAATCCACAGGTCAAGTTGGCAAAAACTGACATACAGCAATGCCAGTTTATTGTTTTGTGATAGCCTTAATCCAGCTAGTTTCTTCACAGGATGATGTTGAAAATATGGGATGCTCATAATCCCTGAATATTTTTTATGTGGATAATTAAACTTGTTCTGGGTGGATGGTTGGATAGCCAGAATAGTAATAACCTCTCTTCCAGCCACTCAAAGAAAATGATATAAACGTAGGGTTGGTTTAATTGTTGAGAGGTCACGTTTTTTCCATTCTTGCTCTCAGGTAAGGAAAGAGCACTGTTGGTTCACGCATTCCTTTTTCCCTCATACACTTTGTTGGGCACTGATATGGTTTGGCTCTGTGTTCCCACCCAAATCTCATGTTGAATTGTGATCCTGAGTGTTGGAGGTGGGGCCTCGCGGGAGACGACTGGATCATGGGGGCGGATTTTCCCCTTGCTGTTCTCATGATAGTGAGTTCTCATGAGATCTGGTTGTTTAAAAGTGTATAGCACTTCCTGCTTCACTCTCTCCCACTCCACCATGTGAAGAAGGTGCCTTTGCCCTTCCGCCACGACTGTGTTTCCTGAGGCCTCCCCAGCCATGCCTCCTGTACAGCCTGCGGAACTGTCAGTTAAACCTCTTTTCTTCATTAATTACCCACTCTCAGGTGGTTTTTTATGGCAGTGTGAGAACGGACTAATACAGAAAATTGGTACCAGAGAAGTGGGATATTGCTATAAAATACCTGAAAATGTGGAAGTGACTTTGGAACTGGGTAATGGGCAGAGGTTGGAACAGTTTGGAGGGCTCAGAAGAAGACAGGAAGATGAGGGAAAGTTTGCAGCTTCCTAGAGACTTGTTGAATGGTTGTGACCAAAGTGCTGATAGTGATATGGACAGTGAAGTCCAGGCTGAGTTGGTCTCAGATGGGAGATGAGAATCTTATTCCGAACTGGAGTGAAGGTCACTCTTGGCTGTGCTTTAGCAAAGAGAGTGGTGGCATTGTGCCCCTGCTCTAGAGATCTGTGAACTCTGAACTCGAGAGGGTATCTGGCAGAAAAAAATTTCTAAGCAGCAAAGTGTTCAAGATGTGGCCTGATTGCTTCTAAAAGCCTATGCTCATTTGCATGAACAAAGTGGAACTTATATTTAAAACAGAAGCTGAGCTTTTATAAAAGTTTGGAGAATTTGCAGCCCAACCATGTGGTGAAAAAGAAAAATCCATTTTCTGGGGAGGTATTCAAGGCTGCAGAAATTTGCATAAGAAGAGCCTCATGTTAACAGCCAAGAGAGTGAGGAAAATGCCTCTAGAGCATTTCAGAGACCTTCACAGCAGCTCCTCCCATCACAGGCATGGAAGCCCAGGAGGAAGAAATGCTTTTGTGGGCCAGCCCAGGGCCCCACTGTTCTGTGCAGCCTTGGGACATGGTGCCCTGCATCCCAGCCACTCCAGCTCCAGCTGTGACTAAAAGGGGCCAAGGTACAGCTTGGGCTGCTGCTTCAGAGGGTGCAAGCCCCAAGCCTTGGTGGCTTCCATGTGGTGTTAGGCAGGTGTGCAGAAGAGTTGAGGTTTAGGAACCTCTACCTAGATTTCAGAGGATGTATGGAAATGCCCGGATGTCCAGGCAGAAGTTTGCTGCAGAGGCAGAGCCCTCATAGATAACCTCTGCGAGGGCAGTGTGGAGGGGAAATGTGGGGTTGGAGCTATGAGAAGAGGGCCACCATCCACCAGACCCCAGAATTGTAGATCCACTGACAGCTTGCACTATGCACCTGTAAAAGTTGCAGGCAGTTAATGCTAGCCTGTGAAAGCAGCTGTGGGGACTATATGCAGAGCCACAGAGGCAGAGCTGCCCAGAGCCTTGGGAGCCCACTCCTTGTGTCAGTGTGGCCTGGATGTGAGACGTGGAGTCAAAGATCATTTTGGAGGTTTGAGATTTAATGACTGCCCTCCTGGATTTTGGACTTGCATGGGGCCCATAGCCCCTTTGTTTTGGCTGATTTCTCCTATTTGGAATGGGAGCATTTACCCAATGCCTGTATCCCCATTGTATCTTGGAGATAACTGACTTGTTTTTGATTTTACAGGCTCACAGGAGGAAGGGACTTGGCTGGTCTCAGATGAGACTTGACTTGGACATTTGAGTTAATGCTGGAATGAGTTAAGACTTTAGGGGGCTATTGGGAAGGCATGATTGTGTTTTGAAATGTGAGGACATGAGATTTGGGAGGGGCCAGGGTGGAATGATATGGTTTGGCTGTGTCCCCCCACCCAAATCTCATGTTGAATTGTGATCCTGAGTCTTGGAGGTAGAGCCTGGTGGGAGGTGATTGGATCATGGGGGCAGATTTCCCCCTTGCTGTTCTCATGACAGTGAGTTCTCATGAGATCTGGTTAAGTGTGTAGCACTTCCCCCTTTGCTTGCTCTCTCCCTCTGCCATGTGAAGAAGGTGCTTGCTTTCCCTTCGCCCTTCTGCCATGACTGTAAGTTTCTTGAGGCCTCGCAGCCATGCTTCCTGTACAGCCTGCAGAACTGTGAGTTAATTAAACCTCTTTTCTT CATSEQ.ID NO. 29 SEQ.ID NO. 74AGCTTTGGGGTTGTCCCTGGACTTGTCTTGGTTCCAGAACCTGACGACCCGGCGACGGCGACGTCTCMPNFSGNWKIIRSENFEELLKVLGVNTTTTGACTAAAAGACAGTGTCCAGTGCTCCAGCCTAGGAGTCTACGGGGACCGCCTCCCGCGCCGCCVMLRKIAVAAASKPAVEIKQEGDTFYACCATGCCCAACTTCTCTGGCAACTGGAAAATCATCCGATCGGAAAACTTCGAGGAATTGCTCAAAGIKTSTTVRTTEINFKVGEEFEEQTVDTGCTGGGGGTGAATGTGATGCTGAGGAAGATTGCTGTGGCTGCAGCGTCCAAGCCAGCAGTGGAGATGRPCKSLVKWESENKMVCEQKLLKGECAAACAGGAGGGAGACACTTTCTACATCAAAACCTCCACCACCGTGCGCACCACAGAGATTAACTTCGPKTSWTRELTNDGELILTMTADDVVAAGGTTGGGGAGGAGTTTGAGGAGCAGACTGTGGATGGGAGGCCCTGTAAGAGCCTGGTGAAATGGGCTRVYVREAGAGTGAGAATAAAATGGTCTGTGAGCAGAAGCTCCTGAAGGGAGAGGGCCCCAAGACCTCGTGGACCAGAGAACTGACCAACGATGGGGAACTGATCCTGACCATGACGGCGGATGACGTTGTGTGCACCAGGGTCTACGTCCGAGAGTGAGTGGCCACAGGTAGAACCGCGGCCGAAGCCCACCACTGGCCATGCTCACCGCCCTGCTTCACTGCCCCCTCCGTCCCACCCCCTCCTTCTAGGATAGCGCTCCCCTTACCCCAGTCACTTCTGGGGGTCACTGGGATGCCTCTTGCAGGGTCTTGCTTTCTTTGACCTCTTCTCTCCTCCCCTACACCAACAAAGAGGAATGGCTGCAAGAGCCCAGATCACCCATTCCGGGTTCACTCCCCGCCTCCCCAAGTCAGCAGTCCTAGCCCCAAACCAGCCCAGAGCAGGGTCTCTCTAAAGGGGACTTGAGGGCCTGAGCAGGAAAGACTGGCCCTCTAGCTTCTACCCTTTGTCCCTGTAGCCTATACAGTTTAGAATATTTATTTGTTAATTTTATTAAAATGCTTTAAAAAAA SEQ.ID NO. 30 SEQ.ID NO. 75CTCGCTTTTCGGTTGCCGTTGTCTTTTTTCCTTGACTCGGAAATGTCCGGTCGTGGTAAGCAGGGTGMSGRGKQGGKARAKAKSRSSRAGLQFGCAAGGCGCGCGCCAAGGCTAAGTCGCGCTCGTCGCGCGCGGGGCTGCAGTTCCCCGTGGGCCGCGTPVGRVHRLLRKGNYSERVGAGAPVYLGCACCGGTTGCTCCGCAAGGGCAACTATTCGGAGCGCGTGGGCGCCGGCGCCCCGGTCTATCTGGCCAAVLEYLTAEILELAGNAARDNKKTRGCGGTGCTCGAGTACTTGACTGCCGAGATCCTGGAGCTTGCCGGCAACGCGGCGCGCGACAACAAGAIIPRHLQLAIRNDEELNKLLGRVTIAAGACGCGCATCATCCCGCGCCACCTGCAGCTGGCCATCCGCAACGACGAGGAGCTCAACAAGCTGCTQGGVLPNIQAVLLPKKTESHHKAKGKGGGCCGCGTGACCATCGCGCAGGGTGGCGTCCTGCCCAACATCCAGGCCGTACTGCTGCCCAAGAAGACGGAGAGCCACCACAAGGCCAAGGGCAAGTGAGGCCGCCCGCCGCCCCCGGGGCCCCTTTGATGGACATAAAGGCTCTTTTCAGAGC CACCTA SEQ.ID NO. 31 SEQ.ID NO. 76ATGTCTGGCCGTGGTAAAGGTGGAAAAGGTTTGGGTAAGGGAGGAGCTAAGCGTCATCGCAAGGTTTMSGRGKGGKGLGKGGAKRHRKVLRDNTGCGCGATAACATCCAGGGCATCACTAAGCCAGCTATCCGGCGCCTTGCTCGTCGCGGCGGTGTCAAIQGITKPAIRRLARRGGVKRISGLIYGCGAATTTCTGGCCTTATCTATGAGGAGACTCGTGGTGTTCTGAAGGTGTTCCTGGAGAACGTGATTEETRGVLKVFLENVIRDAVTYTEHAKCGTGACGCTGTCACTTACACAGAGCACGCCAAACGCAAGACCGTGACAGCAATGGATGTGGTCTACGRKTVTAMDVVYALKRQGRTLYGFGGCGCTGAAGCGACAGGGACGCACTCTTTACGGCTTCGGTGGCTAAGGCTCCTGCTTGCTGCACTCTTATTTTCATTTTCAACCAAAGGCCCTTTTCAGGGCCGCCCA SEQ.ID NO. 32 SEQ.ID NO. 77GCCTCCACAGATATCAAAAGAAACCTGAAGAGCCTACAAAAAAAAAAGAGATAAAGACAAAATTCAAMLFEQGQQALELPECTMQKAAYYENPGAAAACACACACATACATAATTGTGGTCACCTGGAGCCTGGGGGCCGGCCCAGCTCTCTCAGGATTCGLFGGYGYSKTTDTYGYSTPHQPYPPAGCAGACATTGGAGGTGGCAGTGAAGGATACAGTGGTAGTCAATGTTATTTGAGCAGGGTCAGCAGGPAAASSLDTDYPGSACSIQSSAPLRACCCTGGAGCTTCCTGAGTGCACAATGCAGAAGGCTGCTTACTATGAAAACCCAGGACTGTTTGGAGGPAHKGAELNGSCMRPGTGNSQGGGGGCTATGGCTACAGCAAAACTACGGACACTTACGGCTACAGCACCCCCCACCAGCCCTACCCACCCCCTSQPPGLNSEQQPPQPPPPPPTLPPSSGCTGCTGCCAGCTCCCTGGACACTGACTATCCAGGTTCTGCCTGCTCCATCCAGAGCTCTGCCCCTCPTNPGGGVPAKKPKGGPNASSSSATITGAGAGCCCCAGCCCACAAAGGAGCTGAACTCAATGGCAGCTGCATGCGGCCGGGCACTGGGAACAGSKQIFPWMKESRQNSKQKNSCATAGECCAGGGTGGGGGTGGTGGCAGCCAGCCTCCTGGTCTGAACTCAGAGCAGCAGCCACCACAACCCCCTSCEDKSPPGPASKRVRTAYTSAQLVECCTCCACCACCGACCCTGCCCCCATCTTCACCCACCAATCCTGGAGGTGGAGTGCCTGCCAAGAAGCLEKEFHFNRYLCRPRRVEMANLLNLTCCAAAGGTGGGCCCAATGCTTCTAGCTCCTCAGCCACCATCAGCAAGCAGATCTTCCCCTGGATGAAERQIKIWFQNRRMKYKKDQKAKGILHAGAGTCTCGACAGAACTCCAAGCAGAAGAACAGCTGTGCCACTGCAGGAGAGAGCTGCGAGGACAAGSPASQSPERSPPLGGAAGHVAYSGQLAGCCCGCCAGGCCCAGCATCCAAGCGGGTACGCACGGCATACACGAGCGCGCAGCTGGTGGAATTGGPPVPGLAYDAPSPPAFAKSQPNMYGLAAAAGGAATTCCACTTCAACCGCTACTTGTGCCGGCCGCGCCGCGTGGAGATGGCCAACCTGCTGAAAAYTAPLSSCLPQQKRYAAPEFEPHPTCTCACGGAACGCCAGATCAAGATCTGGTTCCAGAACCGGCGCATGAAGTACAAGAAGGACCAGAAGMASNGGGFASANLQGSPVYVGGNFVEGCCAAGGGCATCCTGCACTCGCCGGCTAGCCAGTCCCCTGAGCGCAGCCCACCGCTCGGCGGCGCCGSMAPASGPVFNLGHLSHPSSASVDYSCTGGCCACGTGGCCTACTCCGGCCAGCTGCCGCCAGTGCCCGGCCTGGCCTACGACGCGCCCTCGCCCAAQIPGNHHHGPCDPHPTYTDLSAHGCCTGCTTTCGCCAAATCACAGCCCAATATGTACGGCCTGGCCGCCTACACGGCGCCACTCAGCAGCHSSQGRLPEAPKLTHLTGCCTGCCACAACAGAAGCGCTACGCAGCGCCGGAGTTCGAGCCCCATCCCATGGCGAGCAACGGCGGCGGCTTCGCCAGCGCCAACTTGCAGGGCAGCCCGGTGTACGTGGGCGGCAACTTCGTCGAGTCCATGGCGCCCGCGTCCGGGCCTGTCTTCAACCTGGGCCACCTCTCGCACCCGTCGTCGGCCAGCGTGGACTACAGTTGCGCCGCGCAGATTCCAGGCAACCACCACCATGGACCTTGCGACCCTCATCCCACCTACACAGATCTCTCGGCCCACCACTCGTCTCAGGGACGACTGCCGGAGGCTCCCAAACTGACGCATCTGTAGCGGCCGCCGCCAGCCCGAACTCGCGGCAAAATTACCTCTCTTGCTGTAGTGGTGGGGTAGAGGGTGGGGCCCGCGGGGCAGTTCGGGAACCCCCTTCCCCGCTCTTGCCCTGCCGCCGCCTCCCGGGTCTCAGGCCTCCAGCGGCGGAGGCGCAGGCGACCGGGCCTCCCCTCCATGGGCGTCCTTTGGGTGACTCGCCATAAATCAGCCGCAAGGATCCTTCCCTGTAAATTTGACAGTGCCACATACTGCGGACCAAGGGACTCCAATCTGGTAATGGTGTCCCAAAGGTAAGTCTGAGACCCATCAGCGGCGCGCCCTGCAGAGGGACCAGAGCTTGGAGAGTCTTGGGCCTGGCCCGCGTCTAGCTTAGTTTCAGAGACCTTAATTTATATTCTCCTTCCTGTGCCGTAAGGATTGCATCGGACTAAACTATCTGTATTTATTATTTGAAGCGAGTCATTTCGTTCCCTGATTATTTATCCTTGTCTGAATGTATTTATGTGTATATTTGTAGATTTATCCAGCCGAGCTTAGGAATTCGCTTCCAGGCCGTGGGGGCCACATTTCACCTCCTTAGTCCCCCTGGTCTGAACTAGTTGAGAGAGTAGTTTTGAACAGTCGTAACCGTGGCTGGTGTTTGTAGTTGACATAAAGGATTAAGACCGCAAATTGTCCTTCATGGGTAGAGTCAGGAAGCCCGGTGGCGTGGCACAACACACTTTGGTCATTTCTCAAAAACCACAGTCCTCACCACAGTTTATTGATTTCAAATTGTCTGGTACTATTGGAACAAATATTTAGAATAAAAAAATTTCCCAGTCAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 33 SEQ.ID NO.  78CCAGCCCTGAGATTCCCAGGTGTTTCCATTCGGTGATCAGCACTGAACACAGAACTCACCATGGAGTMEFGLSWVFLVAILKGVQCEVQLVESTTGGACTGAGCTGGGTTTTCCTTGTTGCTATTTTAAAAGGTGTCCAGTGTGAAGTGCAGCTGGTGGAGGVVVQPGGSLRLSCAASGFTFDDYAGTCTGGGGGAGTCGTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCMHWVRQAPGKGLEWVSLISWDGGSTYTTTGATGACTATGCCATGCACTGGGTCCGTCAAGCTCCGGGGAAGGGTCTGGAGTGGGTCTCCCTTAYADSVKGRFTISRDNSKNSLYLQMNSTTAGTTGGGATGGTGGTAGCACCTACTATGCAGACTCTGTGAAGGGTCGATTCACCATCTCCAGAGALRAEDTALYYCATRGGYSTAGFDYWGCAATAGTAAAAATTCCTTGTATCTGCAAATGAACAGTCTGAGAGCTGAGGACACCGCCTTGTATTACQGTLVTVSSASTKGPSVFPLAPSSKSTGTGCAACCCGGGGGGGTTATTCCACCGCCGGCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTSGGTAALGCLVKDYFPEPVTVSWNSTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGALTSGVHTFPAVLQSSGLYSLSSVVGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTVPSSSLGTQTYICNVNHKPSNTKVDTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCKKVEPKSCDKTHTCPPCPAPELLGGPTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCASVFLFPPKPKDTLMISRTPEVTCVVVCAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCDVSHEDPEVKFNWYVDGVEVHNAKTKCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGPREEQYNSTYRVVSVLTVLHQDWLNGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCKEYKCKVSNKALPAPIEKTISKAKGQTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGPREPQVYTLPPSRDELTKNQVSLTCLGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGVKGFYPSDIAVEWESNGQPENNYKTTGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAPPVLDSDGSFFLYSKLTVDKSRWQQGAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGNVFSCSVMHEALHNHYTQKSLSLSPGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGA KGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGAGTGCGACGGCCGGCAAGCCCCCGCTCCCCGGGCTCTCGCGGTCGCACGAGGATGCTTGGCACGTACCCCGTGTACATACTTCCCGGGCGCCCAGCATGGAAATAAAGCACCCAGCGCTGCCCTGGGCCCCTGCGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 34 SEQ.ID NO. 79GAGGGAACCATGGAAACCCCAGCGCAGCTTCTCTTCCTCCTGCTACTCTGGCTCCCAGATATCACCGMETPAQLLFLLLLWLPDITGEIVLTQGAGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGAGAAAGAGCCGCCCTCTCSPGTLSLSPGERAALSCRASQSVNSKATGCAGGGCCAGTCAGAGTGTTAACAGCAAGTACTTAGCCTGGTACCAGCAGAAGCCTGGCCAGGCTYLAWYQQKPGQAPRLLMYAASIRATGCCCAGGCTCCTCATGTATGCTGCATCCATCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGIPDRFSGSGSGTDFTLTISRLESEDFGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAATCTGAGGACTTTGCACTGTATTTCTGALYFCQQYGTSPLTFGGGTKVEIKRTTCAGCAATATGGTACTTCACCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGVAAPSVFIFPPSDEQLKSGTASVVCLGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGLNNFYPREAKVQWKVDNALQSGNSQETGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCASVTEQDSKDSTYSLSSTLTLSKADYEATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCKHKVYACEVTHQGLSSPVTKSFNRGEACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGG CGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAGAGGGAGAAGTGCCCCCACCTGCTCCTCAGTTCCAGCCTGACCCCCTCCCATCCTTTGGCCTCTGACCCTTTTTCCACAGGGGACCTACCCCTATTGCGGTCCTCCAGCTCATCTTTCACCTCACCCCCCTCCTCCTCCTTGGCTTTAATTATGCTAATGTTGGAGGAGAATGAATAAATAAAGTGAATCTTTGCACCTAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 35 SEQ.ID NO. 80ACGCGGGGGGCCCGCTCTCGGCGAGCCCGAGCCGCCGCCGGCCCCGCGGCGGAGATGAGCAGGTCCGMSRSATLLLCLLGCHVWKAVTKTLRECGACGCTGCTGCTGTGCCTGCTGGGCTGCCACGTCTGGAAGGCGGTGACCAAGACGCTGCGGGAGCCPGAGAQEVTLKVHISDASTHQPVADACGGCGCCGGAGCCCAAGAGGTGACGTTAAAGGTGCACATCAGCGACGCCAGCACCCACCAGCCCGTALIEIFTNQASIASGTSGTDGVAFIKFGCAGATGCGCTCATCGAGATCTTCACCAACCAGGCCTCCATAGCCTCTGGCACCTCGGGGACTGATGQYKLGSQLIVTASKHAYVPNSAPWKPGCGTCGCCTTTATCAAGTTCCAGTATAAGCTGGGCAGTCAGTTGATTGTCACCGCCTCGAAGCATGCIRLPVESSLSLGLLPERSATLMVYEDCTACGTGCCAAACTCTGCCCCATGGAAGCCAATCCGGTTACCTGTATTTTCCTCTCTGAGCCTTGGCVVQIVSGFQGARPQPRVHFQRRALRLCTGCTTCCAGAACGCTCTGCCACTCTAATGGTATATGAAGATGTCGTCCAAATAGTATCAGGATTCCPENTSYSDLTAFLTAASSPSEVDSFPAAGGTGCCCGGCCACAGCCTCGCGTTCATTTCCAGAGAAGGGCTCTGAGGTTGCCTGAGAACACCAGYLRGLDGNGTGNSTRHDLTPVTAVSVCTACAGTGACCTGACCGCGTTTCTCACGGCCGCCAGCTCCCCTTCGGAGGTGGACAGTTTTCCTTATHLLSSNGTPVLVDGPIYVTVPLATQSTTGCGAGGATTAGACGGAAATGGAACAGGAAACAGCACCAGGCATGACCTGACCCCAGTCACAGCCGSLRHNAYVAAWRFDQKLGTWLKSGLGTCAGCGTCCACTTGCTGAGCAGTAATGGAACGCCGGTGCTGGTGGATGGTCCCATCTATGTCACTGTLVHQEGSQLTWTYIAPQLGYWVAAMSGCCCCTGGCCACGCAGAGCAGCCTGAGGCACAATGCCTATGTCGCGGCGTGGCGGTTTGACCAGAAGPPIPGPVVTQDITTYHTVFLLAILGGCTGGGAACGTGGCTGAAGAGCGGTCTGGGTCTTGTGCACCAGGAAGGCAGCCAGCTGACGTGGACATMAFILLVLLCLLLYYCRRKCLKPRQHACATTGCCCCCCAGTTGGGGTACTGGGTGGCCGCCATGTCCCCTCCCATCCCAGGTCCCGTTGTAACHRKLQLPAGLESSKRDQSTSMSHINLACAGGACATTACCACGTATCACACGGTGTTTCTTTTGGCCATTTTAGGAGGAATGGCTTTCATACTTLFSRRASEFPGPLSVTSHGRPEAPGTTTGGTTTTGCTGTGTCTCCTTTTATATTATTGCAGGAGGAAGTGCTTGAAACCTCGTCAGCACCACAKELMSGVHLEMMSPGGEGDLHTPMLKGAAAACTGCAGCTCCCTGCAGGACTGGAGAGTTCCAAAAGAGACCAGTCCACGTCCATGTCACACATLSYSTSQEFSSREELLSCKEEDKSQITAACTTGCTGTTTTCACGCCGAGCGTCAGAATTCCCTGGCCCGCTGTCCGTCACCAGCCACGGCCGCSFDNLTPSGTLGKDYHKSVEVFPLKACCCGAGGCCCCCGGCACGAAGGAACTGATGAGTGGAGTCCATTTGGAAATGATGTCTCCGGGCGGCGRKSMEREGYESSGNDDYRGSYNTVLSAAGGGGACCTGCACACCCCCATGCTCAAGCTCTCCTACAGCACCTCCCAGGAATTTAGCTCCCGGGAQPLFEKQDREGPASTGSKLTIQEHLYGGAGCTCCTCTCTTGCAAGGAAGAGGATAAAAGCCAGATCTCCTTTGATAACCTCACTCCAAGTGGGPAPSSPEKEQLLDRRPTECMMSRSVDACGCTGGGGAAAGACTACCATAAGTCAGTGGAGGTTTTTCCCTTAAAGGCAAGAAAATCTATGGAAAHLERPTSFPRPGQLICCSSVDQVNDSGAGAAGGCTACGAGTCCTCGGGCAATGATGACTACAGGGGTAGTTACAACACCGTGCTCTCACAGCCVYRKVLPALVIPAHYMKLPGDHSYVSTTTATTTGAAAAGCAGGACAGAGAAGGTCCAGCCTCCACGGGAAGCAAACTCACCATTCAGGAACATQPLVVPADQQLEIERLQAELSNPHAGCTGTACCCCGCGCCTTCATCACCTGAGAAAGAACAGCTGCTGGACCGCAGACCCACTGAATGTATGAIFPHPSSQIQPQPLSSQAISQQHLQDTGTCGCGATCAGTAGATCACCTCGAGAGACCTACGTCCTTCCCACGGCCCGGCCAGTTAATCTGCTGAGTREWSPQNASMSESLSIPASLNDACAGTTCTGTCGACCAGGTCAATGACAGCGTTTACAGGAAAGTACTGCCTGCCTTGGTCATCCCGGCTALAQMNSEVQLLTEKALMELGGGKPLCATTATATGAAACTCCCCGGGGACCACTCCTATGTCAGCCAGCCCCTCGTCGTCCCGGCTGATCAGCPHPRAWFVSLDGRSNAHVRHSYIDLQAGCTTGAGATAGAAAGACTACAGGCTGAGCTGTCCAATCCCCATGCCGGGATCTTCCCACACCCGTCRAGRNGSNDASLDSGVDMNEPKSARKCTCACAGATCCAGCCCCAGCCCCTGTCTTCCCAGGCCATCTCTCAGCAGCACCTGCAGGATGCGGGCGRGDALSLQQNYPPVQEHQQKEPRAPACCCGGGAGTGGAGCCCTCAGAACGCATCCATGTCGGAGTCTCTCTCCATCCCAGCTTCCCTGAACGDSTAYTQLVYLDDVEQSGSECGTTVCACGCGGCTTTGGCTCAGATGAACAGTGAGGTGCAGCTCCTGACTGAAAAGGCCCTGATGGAGCTTGGTPEDSALRCLLEGSSRRSGGQLPSLQGGGTGGGAAGCCGCTTCCGCACCCCCGGGCGTGGTTCGTCTCCTTGGATGGCAGGTCCAACGCTCACEETTRRTADAPSEPAASPHQRRSAHEGTTAGACATTCATACATTGATCTCCAAAGAGCTGGAAGGAACGGAAGTAATGATGCCAGTTTGGACTEEEDDDDDDQGEDKKSPWQKREERPLCTGGCGTAGATATGAATGAACCAAAATCAGCCCGGAAGGGAAGGGGAGATGCTTTGTCTCTGCAGCAMAFNIKGAACTACCCGCCCGTCCAAGAGCACCAGCAGAAAGAGCCTCGAGCCCCAGACAGCACGGCCTACACGCAGCTCGTGTACCTGGATGACGTGGAACAGAGTGGTAGCGAATGTGGGACCACGGTCTGTACCCCCGAGGACAGTGCCCTGCGATGCTTGTTGGAGGGGTCGAGTCGGAGAAGTGGTGGCCAGCTGCCCAGCCTGCAGGAGGAGACGACCAGACGGACTGCGGATGCCCCCTCGGAGCCAGCAGCCAGCCCCCACCAGAGAAGATCTGCCCACGAGGAAGAGGAAGACGATGATGATGATGACCAAGGAGAAGACAAGAAAAGCCCCTGGCAGAAACGGGAGGAGAGGCCCCTGATGGCGTTTAACATTAAATGAGCTATCGCAGACCCACCTGACTGTGGAATATAAAATTGCCAAATATCCTTTCTCATGGAAGCGCGTACCCGTTCGTGGAGGAAACGGAACGGCAGCCCAGCCGTGGGACGGACGTGGACGTTTACTGCATTCCTGTTTGCCGTGTAAATGTTAGAAAGGAATTAAAGTTATTACTCGGAATAAAGGATGACTTTGGCGGATGTCGCCCCTGCAAGGAGGTGGCTGAAAGTGGTGTCCAGATGTCCTTCCGAGGACTCGGCGTATCCGCCACCAGGGACATTAAGAAACCGCACGTGATGTCGCTATGCTCTAACGATCACCTCAGTTCTCCCTCGGATTCTGGGAACAGATGAAACTTTTTGCATCGCTTGAGTCATTTTTATCACAATAATCCTACTGTGAAGCTGTCGTTGAGAACTTAGGTTGGCACGTAGCGTCTCAAGGTATGCGTTCTCTCAAAGGAAAGCTATGCATCGCTGCTTCTTTGTCTGATTTTGCTTAGATTTTGCTTTGGTTAGGTTGCGTTTTGGGGTTTGCCTTTTTTTGTTGTCGCTTAAATGCAATTTGGTTGTAAAGATTTGATTCCTTTGTGTTCATCTGTTCCGCTTCTCAGCGGTCCATCTCAGCGTCTCCCTTCAGGAACCGCTGAGTGTCCTCTCTTAACATCCAAGCCTTTTAATGAAATCGTACTGAAATCTGTATCAGCTAAGAGTCCTCCAATCCTGGTCCCATTAACTCCAAGTGCCTTTTTGTCAGTGACAACAGACAGTCCCTCGCTTTTTGTTGTTGTTGGTTTTCTTAACCCCTTTAATGGAACTGCCTGGATTTTATACAGTTATTAAAGGATGTCTCTTTTGCTTTAAACTGCATGCTGCCAAGTGCCATTTGGGGTCAGCATCCTCGTTTCAACACAGTGTGCTCTCTAGTTATCATGTGTAACGTGGGTTCTGTTTAGCGAAGATAGACTAGAGGACACGTTAGAGATGCCCTTCCCTGCTCCATCCCTGTGGCACCATTATGGTTTTTTGGCTGTTTGTATATACGGTTACGTATTAACTCTGGAATCCTATGGGCTCATCTTGCTCACCCAATGTGGGAGTCTGGTTTGAGCAAGCGAGCTGAATGTGACTATTAAAAAAAATTTAAAAAAAAAAAAGAAAATCTTATGTACTATCCAAAAGTGCCAGAATGACTCTTCTGTGCATTCTTCTTAAAGAGCTGCTTGGTTATCCAAAAATGAAAATTCAAAATAAACTCTGAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 36SEQ.ID NO. 81CGTCACTTCCTGTTGCCTTAGGGGAACGTGGCTTTCCCTGCAGAGCCGGTGTCTCCGCCTGCGTCCCMDSALSDPHNGSAEAGGPTNSTTRPPTGCTGCAGCAACCGGAGCTGGAGTCGGATCCCGAACGCACCCTCGCCATGGACTCGGCCCTCAGCGASTPEGIALAYGSLLLMALLPIFFGALTCCGCATAACGGCAGTGCCGAGGCAGGCGGCCCCACCAACAGCACTACGCGGCCGCCTTCCACGCCCRSVRCARGKNASDMPETITSRDAARFGAGGGCATCGCGCTGGCCTACGGCAGCCTCCTGCTCATGGCGCTGCTGCCCATCTTCTTCGGCGCCCPIIASCTLLGLYLFFKIFSQEYINLLTGCGCTCCGTACGCTGCGCCCGCGGCAAGAATGCTTCAGACATGCCTGAAACAATCACCAGCCGGGALSMYFFVLGILALSHTISPFMNKFFPTGCCGCCCGCTTCCCCATCATCGCCAGCTGCACACTCTTGGGGCTCTACCTCTTTTTCAAAATATTCASFPNRQYQLLFTQGSGENKEEIINYTCCCAGGAGTACATCAACCTCCTGCTGTCCATGTATTTCTTCGTGCTGGGAATCCTGGCCCTGTCCCEFDTKDLVCLGLSSIVGVWYLLRKHWACACCATCAGCCCCTTCATGAATAAGTTTTTTCCAGCCAGCTTTCCAAATCGACAGTACCAGCTGCTIANNLFGLAFSLNGVELLHLNNVSTGCTTCACACAGGGTTCTGGGGAAAACAAGGAAGAGATCATCAATTATGAATTTGACACCAAGGACCTGCILLGGLFIYDVFWVFGTNVMVTVAKGTGTGCCTGGGCCTGAGCAGCATCGTTGGCGTCTGGTACCTGCTGAGGAAGCACTGGATTGCCAACASFEAPIKLVFPQDLLEKGLEANNFAMACCTTTTTGGCCTGGCCTTCTCCCTTAATGGAGTAGAGCTCCTGCACCTCAACAATGTCAGCACTGGLGLGDVVIPGIFIALLLRFDISLKKNCTGCATCCTGCTGGGCGGACTCTTCATCTACGATGTCTTCTGGGTATTTGGCACCAATGTGATGGTGTHTYFYTSFAAYIFGLGLTIFIMHIFACAGTGGCCAAGTCCTTCGAGGCACCAATAAAATTGGTGTTTCCCCAGGATCTGCTGGAGAAAGGCCKHAQPALLYLVPACIGFPVLVALAKGTCGAAGCAAACAACTTTGCCATGCTGGGACTTGGAGATGTCGTCATTCCAGGGATCTTCATTGCCTTEVTEMFSYESSAEILPHTPRLTHFPTGCTGCTGCGCTTTGACATCAGCTTGAAGAAGAATACCCACACCTACTTCTACACCAGCTTTGCAGCCVSGSPASLADSMQQKLAGPRRRRPQNTACATCTTCGGCCTGGGCCTTACCATCTTCATCATGCACATCTTCAAGCATGCTCAGCCTGCCCTCC PSAMTATACCTGGTCCCCGCCTGCATCGGTTTTCCTGTCCTGGTGGCGCTGGCCAAGGGAGAAGTGACAGAGATGTTCAGCTACGAGTCCTCGGCGGAAATCCTGCCTCATACCCCGAGGCTCACCCACTTCCCCACAGTCTCGGGCTCCCCAGCCAGCCTGGCCGACTCCATGCAGCAGAAGCTAGCTGGCCCTCGCCGCCGGCGCCCGCAGAATCCCAGCGCCATGTAATGCCCAGCGGGTGCCCACCTGCCCGCTTCCCCCTACTGCCCCGGGGCCCAAGTTATGAGGAGTCAAATCCTAAGGATCCAGCGGCAGTGACAGAATCCAAAGAGGGAACAGAGGCATCAGCATCGAAGGGGCTGGAGAAGAAAGAGAAATGATGCAGCTGGTGCCCGAGCCTCTCAGGGCCAGACCAGACAGATGGGGGCTGGGCCCACACAGGCGTGCACCGGTAGAGGGCACAGGAGGCCAAGGGCAGCTCCAGGACAGGGCAGGGGGCAGCAGGATACCTCCAGCCAGGCCTCTGTGGCCTCTGTTTCCTTCTCCCTTTCTTGGCCCTCCTCTGCTCCTCCCCACACCCTGCAGGCAAAAGAAACCCCCAGCTTCCCCCCTCCCCGGGAGCCAGGTGGGAAAAGTGGGTGTGATTTTTAGATTTTGTATTGTGGACTGATTTTGCCTCACATTAAAAACTCATCCCATGGCCAGGGCGGGCCACTGTGCTCCTGGAAAAAAAAAASEQ.ID NO. 37 STAR clone:TGCCTCAGTCTCTCACTGTGCCTTATGCCCCTCAGCTGAATTCTTTCTTCTGAGCAGGCAGGAATTGAGGTTGCTGCAGACGTGTATGCATTTGCCACCAGTAACATACTTTGGTGCCACATGACTAGGATATGTTCTCTAGTGCTAACATGTTCGTTTACAGTTCTTAGGACTCCCTGATAGAAAAAAACACAAAAAAAAACACAAAAAAACCCAACCA SEQ.ID NO. 38 SEQ.ID NO. 82GTTGGGAAAGAGCAGCCTGGGCGGCAGGGGCGGTGGCTGGAGCTCGGTAAAGCTCGTGGGACCCCATMVCGSPGGMLLLRAGLLALAALCLLRTGGGGGAATTTGATCCAAGGAAGCGGTGATTGCCGGGGGAGGAGAAGCTCCCAGATCCTTGTGTCCAVPGARAAACEPVRIPLCKSLPWNMTKCTTGCAGCGGGGGAGGCGGAGACGGCGGAGCGGGCCTTTTGGCGTCCACTGCGCGGCTGCACCCTGCMPNHLHHSTQANAILAIEQFEGLLGTCCCATCCTGCCGGGATCATGGTCTGCGGCAGCCCGGGAGGGATGCTGCTGCTGCGGGCCGGGCTGCTHCSPDLLFFLCAMYAPICTIDEQHEPTGCCCTGGCTGCTCTCTGCCTGCTCCGGGTGCCCGGGGCTCGGGCTGCAGCCTGTGAGCCCGTCCGCIKPCKSVCERARQGCEPILIKYRHSWATCCCCCTGTGCAAGTCCCTGCCCTGGAACATGACTAAGATGCCCAACCACCTGCACCACAGCACTCPENLACEELPVYDRGVCISPEAIVTAAGGCCAACGCCATCCTGGCCATCGAGCAGTTCGAAGGTCTGCTGGGCACCCACTGCAGCCCCGATCTDGADFPMDSSNGNCRGASSERCKCKPGCTCTTCTTCCTCTGTGCCATGTACGCGCCCATCTGCACCATTGACTTCCAGCACGAGCCCATCAAGIRATQKTYFRNNYNYVIRAKVKEIKTCCCTGTAAGTCTGTGTGCGAGCGGGCCCGGCAGGGCTGTGAGCCCATACTCATCAAGTACCGCCACTKCHDVTAVVEVKEILKSSLVNIPRDTCGTGGCCGGAGAACCTGGCCTGCGAGGAGCTGCCAGTGTACGACAGGGGCGTGTGCATCTCTCCCGAVNLYTSSGCLCPPLNVNEEYIIMGYEGGCCATCGTTACTGCGGACGGAGCTGATTTTCCTATGGATTCTAGTAACGGAAACTGTAGAGGGGCADEERSRLLLVEGSIAEKWKDRLGKKVAGCAGTGAACGCTGTAAATGTAAGCCTATTAGAGCTACACAGAAGACCTATTTCCGGAACAATTACAKRWDMKLRHLGLSKSDSSNSDSTQSQACTATGTCATTCGGGCTAAAGTTAAAGAGATAAAGACTAAGTGCCATGATGTGACTGCAGTAGTGGAKSGRNSNPRQARNGGTGAAGGAGATTCTAAAGTCCTCTCTGGTAAACATTCCACGGGACACTGTCAACCTCTATACCAGCTCTGGCTGCCTCTGCCCTCCACTTAATGTTAATGAGGAATATATCATCATGGGCTATGAAGATGAGGAACGTTCCAGATTACTCTTGGTGGAAGGCTCTATAGCTGAGAAGTGGAAGGATCGACTCGGTAAAAAAGTTAAGCGCTGGGATATGAAGCTTCGTCATCTTGGACTCAGTAAAAGTGATTCTAGCAATAGTGATTCCACTCAGAGTCAGAAGTCTGGCAGGAACTCGAACCCCCGGCAAGCACGCAACTAAATCCCGAAATACAAAAAGTAACACAGTGGACTTCCTATTAAGACTTACTTGCATTGCTGGACTAGCAAAGGAAAATTGCACTATTGCACATCATATTCTATTGTTTACTATAAAAATCATGTGATAACTGATTATTACTTCTGTTTCTCTTTTGGTTTCTGCTTCTCTCTTCTCTCAACCCCTTTGTAATGGTTTGGGGGCAGACTCTTAAGTATATTGTGAGTTTTCTATTTCACTAATCATGAGAAAAACTGTTCTTTTGCAATAATAATAAATTAAACATGCTGTTACCAGAGCCTCTTTGCTGGAGTCTCCAGATGTTAATTTACTTTCTGCACCCCAATTGGGAATGCAATATTGGATGAAAAGAGAGGTTTCTGGTATTCACAGAAAGCTAGATATGCCTTAAAACATACTCTGCCGATCTAATTACAGCCTTATTTTTGTATGCCTTTTGGGCATTCTCCTCATGCTTAGAAAGTTCCAAATGTTTATAAAGGTAAAATGGCAGTTTGAAGTCAAATGTCACATAGGCAAAGCAATCAAGCACCAGGAAGTGTTTATGAGGAAACAACACCCAAGATGAATTATTTTTGAGACTGTCAGGAAGTAAAATAAATAGGAGCTTAAGAAAGAACATTTTGCCTGATTGAGAAGCACAACTGAAACCAGTAGCCGCTGGGGTGTTAATGGTAGCATTCTTCTTTTGGCAATACATTTGATTTGTTCATGAATATATTAATCAGCATTAGAGAAATGAATTATAACTAGACATCTGCTGTTATCACCATAGTTTTGTTTAATTTGCTTCCTTTTAAATAAACCCATTGGTGAAAGTCCCAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 39SEQ,ID NO. 83ACTGAAAGCTCCGGTGCCAGACCCCACCCCCGGCCCCGGCCCGGGACCCCCTCCCCTCCCGGGATCCMKTSPRRPLILKRRRLPLPVQNAPSECCCGGGGTTCCCACCCCGCCCGCACCGCCGGGGACCCGGCCGGTCCGGCGCGAGCCCCCGTCCGGGGTSEEEPKRSPAQQESNQAEASKEVAECCCTGGCTCGGCCCCCAGGTTGGAGGAGCCCGGAGCCCGCCTTCGGAGCTACGGCCTAACGGCGGCGSNSCKFPAGIKIINHPTMPNTQVVAIGCGACTGCAGTCTGGAGGGTCCACACTTGTGATTCTCAATGGAGAGTGAAAACGCAGATTCATAATGPNNANIHSIITALTAKGKESGSSGPNAAAACTAGCCCCCGTCGGCCACTGATTCTCAAAAGACGGAGGCTGCCCCTTCCTGTTCAAAATGCCCKFILISCGGAPTQPPGLRPQTQTSYDCAAGTGAAACATCAGAGGAGGAACCTAAGAGATCCCCTGCCCAACAGGAGTCTAATCAAGCAGAGGCAKRTEVTLETLGPKPAARDVNLPRPPCTCCAAGGAAGTGGCAGAGTCCAACTCTTGCAAGTTTCCAGCTGGGATCAAGATTATTAACCACCCCGALCEQKRETCADGEAAGCTINNSLSACCATGCCCAACACGCAAGTAGTGGCCATCCCCAACAATGCTAATATTCACAGCATCATCACAGCACNIQWLRKMSSDGLGSRSIKQEMEEKETGACTGCCAAGGGAAAAGAGAGTGGCAGTAGTGGGCCCAACAAATTCATCCTCATCAGCTGTGGGGGNCHLEQRQVKVEEPSRPSASWQNSVSAGCCCCAACTCAGCCTCCAGGACTCCGGCCTCAAACCCAAACCAGCTATGATGCCAAAAGGACAGAAERPPYSYMAMIQFAINSTERKRMTLKGTGACCCTGGAGACCTTGGGACCAAAACCTGCAGCTAGGGATGTGAATCTTCCTAGACCACCTGGAGDIYTWIEDHFPYFKHIAKPGWKNSIRCCCTTTGCGAGCAGAAACGGGAGACCTGTGCAGATGGTGAGGCAGCAGGCTGCACTATCAACAATAGHNLSLHDMFVRETSANGKVSFWTIHPCCTATCCAACATCCAGTGGCTTCGAAAGATGAGTTCTGATGGACTGGGCTCCCGCAGCATCAAGCAASANRYLTLDQVFKQQKRPNPELRRNMGAGATGGAGGAAAAGGAGAATTGTCACCTGGAGCAGCGACAGGTTAAGGTTGAGGAGCCTTCGAGACTIKTELPLGARRKMKPLLPRVSSYLVCATCAGCGTCCTGGCAGAACTCTGTGTCTGAGCGGCCACCCTACTCTTACATGGCCATGATACAATTPIQFPVNQSLVLQPSVKVPLPLAASLCGCCATCAACAGCACTGAGAGGAAGCGCATGACTTTGAAAGACATCTATACGTGGATTGAGGACCACMSSELARHSKRVRIAPKVLLAEEGIATTTCCCTACTTTAAGCACATTGCCAAGCCAGGCTGGAAGAACTCCATCCGCCACAACCTTTCCCTGCPLSSAGPGKEEKLLFGEGFSPLLPVQACGACATGTTTGTCCGGGAGACGTCTGCCAATGGCAAGGTCTCCTTCTGGACCATTCACCCCAGTGCTIKEEEIQPGEEMPHLARPIKVESPPCAACCGCTACTTGACATTGGACCAGGTGTTTAAGCAGCAGAAACGACCGAATCCAGAGCTCCGCCGGLEEWPSPAPSFKEESSHSWEDSSQSPAACATGACCATCAAAACCGAACTCCCCCTGGGCGCACGGCGGAAGATGAAGCCACTGCTACCACGGGTPRPKKSYSGLRSPTRCVSEMLVIQHTCAGCTCATACCTGGTACCTATCCAGTTCCCGGTGAACCAGTCACTGGTGTTGCAGCCCTCGGTGAARERRERSRSRRKQHLLPPCVDEPELLGGTGCCATTGCCCCTGGCGGCTTCCCTCATGAGCTCAGAGCTTGCCCGCCATAGCAAGCGAGTCCGCFSEGPSTSRWAAELPFPADSSDPASQATTGCCCCCAAGGTGCTGCTAGCTGAGGAGGGGATAGCTCCTCTTTCTTCTGCAGGACCAGGGAAAGLSYSQEVGGPFKTPIKETLPISSTPSAGGAGAAACTCCTGTTTGGAGAAGGGTTTTCTCCTTTGCTTCCAGTTCAGACTATCAAGGAGGAAGAKSVLPRTPESWRLTPPAKVGGLDFSPAATCCAGCCTGGGGAGGAAATGCCACACTTAGCGAGACCCATCAAAGTGGAGAGCCCTCCCTTGGAAVQTSQGASDPLPDPLGLMDLSTTPLQGAGTGGCCCTCCCCGGCCCCATCTTTCAAAGAGGAATCATCTCACTCCTGGGAGGATTCGTCCCAATSAPPLESPQRLLSSEPLDLISVPFGNCTCCCACCCCAAGACCCAAGAAGTCCTACAGTGGGCTTAGGTCCCCAACCCGGTGTGTCTCGGAAATSSPSDIDVPKPGSPEPQVSGLAANRSGCTTGTGATTCAACACAGGGAGAGGAGGGAGAGGAGCCGGTCTCGGAGGAAACAGCATCTACTGCCTLTEGLVLDTMNDSLSKILLDISFPGLCCCTGTGTGGATGAGCCGGAGCTGCTCTTCTCAGAGGGGCCCAGTACTTCCCGCTGGGCCGCAGAGCDEDPLGPDNINWSQFIPELQTCCCGTTCCCAGCAGACTCCTCTGACCCTGCCTCCCAGCTCAGCTACTCCCAGGAAGTGGGAGGACCTTTTAAGACACCCATTAAGGAAACGCTGCCCATCTCCTCCACCCCGAGCAAATCTGTCCTCCCCAGAACCCCTGAATCCTGGAGGCTCACGCCCCCAGCCAAAGTAGGGGGACTGGATTTCAGCCCAGTACAAACCTCCCAGGGTGCCTCTGACCCCTTGCCTGACCCCCTGGGGCTGATGGATCTCAGCACCACTCCCTTGCAAAGTGCTCCCCCCCTTGAATCACCGCAAAGGCTCCTCAGTTCAGAACCCTTAGACCTCATCTCCGTCCCCTTTGGCAACTCTTCTCCCTCAGATATAGACGTCCCCAAGCCAGGCTCCCCGGAGCCACAGGTTTCTGGCCTTGCAGCCAATCGTTCTCTGACAGAAGGCCTGGTCCTGGACACAATGAATGACAGCCTCAGCAAGATCCTGCTGGACATCAGCTTTCCTGGCCTGGACGAGGACCCACTGGGCCCTGACAACATCAACTGGTCCCAGTTTATTCCTGAGCTACAGTAGAGCCCTGCCCTTGCCCCTGTGCTCAAGCTGTCCACCATCCCGGGCACTCCAAGGCTCAGTGCACCCCAAGCCTCTGAGTGAGGACAGCAGGCAGGGACTGTTCTGCTCCTCATAGCTCCCTGCTGCCTGATTATGCAAAAGTAGCAGTCACACCCTAGCCACTGCTGGGACCTTGTGTTCCCCAAGAGTATCTGATTCCTCTGCTGTCCCTGCCAGGAGCTGAAGGGTGGGAACAACAAAGGCAATGGTGAAAAGAGATTAGGAACCCCCCAGCCTGTTTCCATTCTCTGCCCAGCAGTCTCTTACCTTCCCTGATCTTTGCAGGGTGGTCCGTGTAAATAGTATAAATTCTCCAAATTATCCTCTAATTATAAATGTAAGCTTATTTCCTTAGATCATTATCCAGAGACTGCCAGAAGGTGGGTAGGATGACCTGGGGTTTCAATTGACTTCTGTTCCTTGCTTTTAGTTTTGATAGAAGGGAAGACCTGCAGTGCACGGTTTCTTCCAGGCTGAGGTACCTGGATCTTGGGTTCTTCACTGCAGGGACCCAGACAAGTGGATCTGCTTGCCAGAGTCCTTTTTGCCCCTCCCTGCCACCTCCCCGTGTTTCCAAGTCAGCTTTCCTGCAAGAAGAAATCCTGGTTAAAAAAGTCTTTTGTATTGGGTCAGGAGTTGAATTTGGGGTGGGAGGATGGATGCAACTGAAGCAGAGTGTGGGTGCCCAGATGTGCGCTATTAGATGTTTCTCTGATAATGTCCCCAATCATACCAGGGAGACTGGCATTGACGAGAACTCAGGTGGAGGCTTGAGAAGGCCGAAAGGGCCCCTGACCTGCCTGGCTTCCTTAGCTTGCCCCTCAGCTTTGCAAAGAGCCACCCTAGGCCCCAGCTGACCGCATGGGTGTGAGCCAGCTTGAGAACACTAACTACTCAATAAAAGCGAAGGTGGACAAAAAAAAAAAAAAAAAA AAASEQ.ID NO. 40 SEQ.ID NO. 84GTCGAGGCTGCGGCGCGTGGGGAGCGGGCGGAGCGGGGGCGGGGGCCGAGCGCGGGGCACCCGGGGGMGSCSGRCALVVLCAFQLVAALERQVCCTCCTGTATAGGCGGGCACCATGGGCTCCTGCTCCGGCCGCTGCGCGCTCGTCGTCCTCTGCGCTTFDFLGYQWAPILANFVHIIIVILGLFTTCAGCTGGTCGCCGCCCTGGAGAGGCAGGTGTTTGACTTCCTGGGCTACCAGTGGGCGCCCATCCTGTIQYRLRYVMVYTLWAAVWVTWNVFGGCCAACTTTGTCCACATCATCATCGTCATCCTGGGACTCTTCGGCACCATCCAGTACCGGCTGCGCIICFYLEVGGLLKDSELLTFSLSRHRTATGTCATGGTGTACACGCTGTGGGCAGCCGTCTGGGTCACCTGGAACGTCTTCATCATCTGCTTCTSWWRERWPGCLHEEVPAVGLGAPHGQACCTGGAAGTCGGTGGCCTCTTAAAGGACAGCGAGCTACTGACCTTCAGCCTCTCCCGGCATCGCTCALVSGAGCALEPSYVEALHSCLQILICTGGTGGCGTGAGCGCTGGCCAGGCTGTCTGCATGAGGAGGTGCCAGCAGTGGGCCTCGGGGCCCCCALLGFVCGCQVVSVFTDEEDSFDFIGCATGGCCAGGCCCTGGTGTCAGGTGCTGGCTGTGCCCTGGAGCCCAGCTATGTGGAGGCCCTACACAGFDPFPLYHVNEKPSSLLSKQVYLPAGTTGCCTGCAGATCCTGATCGCGCTTCTGGGCTTTGTCTGTGGCTGCCAGGTGGTCAGCGTGTTTACGGATGAAGAGGACAGCTTTGATTTCATTGGTGGATTTGATCCATTTCCTCTCTACCATGTCAATGAAAAGCCATCCAGTCTCTTGTCCAAGCAGGTGTACTTGCCTGCGTAAGTGAGGAAACAGCTGACCCTGCTCCTGTGGCCTCCAGCCTCAGCGACCGACCAGTGACAATGACAGGAGCTCCCAGGCCTTGGGACGCGCCCCCACCCAGCACCCCCCAGGCGGCCGGCAGCACCTGCCCTGGGTTCTAAGTACTGGACACCAGCCAGGGCGGCAGGGCAGTGCCACGGCTGGCTGCAGCGTCAAGAGAGTTTGTAATTTCCTTTCTCTTAAAAAAAAAAAAGAAAAGAAAACATACAAAAGAAAAGGCAAAACCCCACATGCCCACCTCCTCTGGCAACATGGGGGTCACAGCTCTGCCCCCAGGCTGTCGTCTCGTCGAGGAGCCCCTCCCTCAGGTGCCAACCTGGGGCTGCTGGACCCTCGGGCTGCAAGCACTGCTGCTGGGATGCAGCCTCCCCAGGAAGTCAATGTGAGGCCCGAGACCCCTCAAGCGGTGAGGGCCCCTGTTGAACATGGAGGGTTCCTAACCCCAAACTCGTGCCAGAAGAACCCCCACCCCACCCAGGAGCTGAGGCTGATGGAGCCCTAGGGTGGGGGCTGGGCTTGACCAGGAACAGCAGAGCCAGGCCCCAAGGCATAGGGCAGGGCACATGGTGGTGACGAGCAGGCAGTACTCTTGTAAAGGGGGCTCTTGGGCAAACAGTCCCAAAGGCTCCCCCAGGTATCATCAAGTTGGTAAATAAACAGGAACATGGCCCAAAAAAAAAAAAAAAA SEQ.ID NO. 41 STAR clone:AAAAAATAAGTATATCTGTCNAGAATCNTATTTATGTGAGATGTGTCAATACTGGTCTTGCGTTATTTCGGCTACTTGAAAATAAGTTAAAAAAGATAGTGTTTGGTTCCAAAAAGGAAAAGTCAGCCTCTCCTGCNTGAGTGGGAGCTGCAACCTTTTAGAATTGATAATCACAAACCCCTCAGACCCAAAGTGGAATAAAGAAAAATATGTAACATTAGGCATTGATGGAAAAGGACTAGATCCTAGTGTAAGCATCCTAATAAAAGGAGAGGTTCACAA SEQ.ID NO. 42 SEQ.ID NO. 85GCAGCCAGATCTGCTGGGACACCTTTCCCAAGGAAGAGCCCGTTGCACTGGGCTTTGAAGGATAAGCMCVSSSSSSHDEAPVLNDKHLDVPDIAGGAGCTTGTTACTCAGGCAGAGGAAGAAAGAGCATCCCAGGCGGGGGGAGCAGCATATGCAAAGGCIITPPTPTGMMLPRDLGSTVWLDETGACGAAGGGGCCCCAGGAGCCTAGGGAGTCTGGGGAAGTGTGAGCACTTTGGAGAGTGGAGGCTGGAGSCPDDGEIDPEACGCTGTGGAGAGTGGGGGCTGGTGGCCGGGAATGAAGCTGCAGCTGGCTGGGCCACATGGTAAAGGCTGACAACTGGACCCAGAGGCCAACTAGCCTATGATCAGCATTTCCCAAAATCTGTTTCCCGACTCATGGTTCTGTGAGATGTGACAAGGGCTCCTTTTTCATTCCTGAGACGCCGGTTTTCATCTGTGATGCGGGGACAGCTGCGCTCCTTGCTGCGAGGCGTCAGGACCCAGGTGATAGTGAAGGGAGGGTGGCGCCCGCGGTTCCCGGCGGCCACTGATGCCTGTCTCTCTGTCGTGTGTACGTGCGTGTGTGCTCCACGCCTGGCTTCTCAGGCTTTCAAATGTGTGTCAGCAGCAGCAGCAGCAGCCACGACGAGGCCCCCGTCCTGAACGACAAGCACCTGGACGTGCCCGACATCATCATCACGCCCCCCACCCCCACGGGCATGATGCTGCCGAGGGACTTGGGGAGCACAGTCTGGCTGGATGAGACAGGGTCGTGCCCAGATGATGGAGAAATCGACCCAGAAGCCTGAGGAGGTGTCCTGGGTTTGGCTGGCTGGCTCCTGCTCCAGCGGCCCGGCTTCAGGTGTCCGGGGGCGTGGCTGCCTGGAGCAGGTGTGCTGAATACCCTGGATGGGAACTGAGCGAACCCGGGCCTCCGCTCAGAGAGACGTGGCAGGACCAGCGAGGAATCCAGCCTGTCCACTTCCAGAACAGTGTTTCCCAGGCCCCGCTGAGTGGACCGGACCTCTGACACCTCCAGGTTCTTGCTGACTCCGGCCTGGTGAAAGGGAGCGCCATGGTCCTGGCTGTTGGGGTCCCAGGGAGAGGCTCTCTTCTGGACAAACACACCCTCCCAGCCCCCAGGGCTGTGCAAACACATGCCCCTCCCATAAGCACCAACAAGAACTTCTTGCAGGTGGAGTGGCTGTTTTTTATAAGTTGTTTTACAGATACGGAAACAGTCCAAAATGGGATTTATAATTTCTTTTTTGCATTATAAATAAAGATCCTCTGTAACAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 43SEQ.ID NO. 86GCGAAGTGAAGGGTGGCCCAGGTGGGGCCAGGCTGACTGAATGTATCTCCTAGCTATGGACTAAATAMDTMMLNVRNLFEQLVRRVEILSEGNATACATGGGGGGAAATAAACAAGTATTCATGAGGGTGAAAATGTGACCCAGCAGGAAAATTACAACTEVQFIQLAKDFEDFRKKWQRTDHELGATTTTCAATTGACGTTGAATAGGATGAGTCATGGAATTTAAGTGATTTACTGAAGATTATACTACTGKYKDLLMKAETERSALDVKLKHARNQGTAGATAGAAGAGCTAAAGAAAGATGGATACTATGATGCTGAATGTGCGGAATCTGTTTGAGCAGCTVDVEIKRRQRAEADCEKLERQIQLIRTGTGCGCCGGGTGGAGATTCTCAGTGAAGGAAATGAAGTCCAATTTATCCAGTTGGCGAAGGACTTTEMLMCDTSGSIQLSEEQKSALAFLNRGAGGATTTCCGTAAAAAGTGGCAGAGGACTGACCATGAGCTGGGGAAATACAAGGATCTTTTGATGAGQPSSSNAGNKRLSTIDESGSILSDIAAGCAGAGACTGAGCGAAGTGCTCTGGATGTTAAGCTGAAGCATGCACGTAATCAGGTGGATGTAGASFDKTDESLDWDSSLVKTFKLKKREKGATCAAACGGAGACAGAGAGCTGAGGCTGACTGCGAAAAGCTGGAACGACAGATTCAGCTGATTCGARRSTSRQFVDGPPGPVKKTRSIGSAVGAGATGCTCATGTGTGACACATCTGGCAGCATTCAACTAAGCGAGGAGCAAAAATCAGCTCTGGCTTDQGNESIVAKTTVTVPNDGGPIEAVSTTCTCAACAGAGGCCAACCATCCAGCAGCAATGCTGGGAACAAAAGACTATCAACCATTGATGAATCTIETVPYWTRSRRKTGTLQPWNSDSTTGGTTCCATTTTATCAGATATCAGCTTTGACAAGACTGATGAATCACTGGATTGGGACTCTTCTTTGLNSRQLEPRTETDSVGTPQSNGGMRLGTGAAGACTTTCAAACTGAAGAAGAGAGAAAAGAGGCGCTCTACTAGCCGACAGTTTGTTGATGGTCHDEVSKTVIKPESCVPCGKRIKEGKLCCCCTGGACCTGTAAAGAAAACTCGTTCCATTGGCTCTGCAGTAGACCAGGGGAATGAATCCATAGTSLKCRDCRVVSHPECRDRCPLPCIPTTGCAAAAACTACAGTGACTGTTCCCAATGATGGCGGGCCCATCGAAGCTGTGTCCACTATTGAGACTLIGTPVKIGEGMLADFVSQTSPMIPSGTGCCATATTGGACCAGGAGCCGAAGGAAAACAGGTACTTTACAACCTTGGAACAGTGACTCCACCCIVVHCVNEIEQRGLTETGLYRISGCDTGAACAGCAGGCAGCTGGAGCCAAGAACTGAGACAGACAGTGTGGGCACGCCACAGAGTAATGGAGGRTVKELKEKFLRVKTVPLLSKVDDIHGATGCGCCTGCATGACTTTGTTTCTAAGACGGTTATTAAACCTGAATCCTGTGTTCCATGTGGAAAGAICSLLKDFLRNLKEPLLTFRLNRAFCGGATAAAATTTGGCAAATTATCTCTGAAGTGTCGAGACTGTCGTGTGGTCTCTCATCCAGAATGTCMEAAEITDEDNSIAAMYQAVGELPQAGGGACCGCTGTCCCCTTCCCTGCATTCCTACCCTGATAGGAACACCTGTCAAGATTGGAGAGGGAATNRDTLAFLMIHLQRVAQSPHTKMDVAGCTGGCAGACTTTGTGTCCCAGACTTCTCCAATGATCCCCTCCATTGTTGTGCATTGTGTAAATGAGNLAKVFGPTIVAHAVPNPDPVTMLQDATTGAGCAAAGAGGTCTGACTGAGACAGGCCTGTATAGGATCTCTGGCTGTGACCGCACAGTAAAAGIKRQPKVVERLLSLPLEYWSQFMMVEAGCTGAAAGAGAAATTCCTCAGAGTGAAAACTGTACCCCTCCTCAGCAAAGTGGATGATATCCATGCQENIDPLHVIENSNAFSTPQTPDIKVTATCTGTAGCCTTCTAAAAGACTTTCTTCGAAACCTCAAAGAACCTCTTCTGACCTTTCGCCTTAACSLLGPVTTPEHQLLKTPSSSSLSQRVAGAGCCTTTATGGAAGCAGCAGAAATCACAGATGAAGACAACAGCATAGCTGCCATGTACCAAGCTGRSTLTKNTPRFGSKSKSATNLGRQGNTTGGTGAACTGCCCCAGGCCAACAGGGACACATTAGCTTTCCTCATGATTCACTTGCAGAGAGTGGCFFASPMLKTCAGAGTCCACATACTAAAATGGATGTTGCCAATCTGGCTAAAGTCTTTGGCCCTACAATAGTGGCCCATGCTGTGCCCAATCCAGACCCAGTGACAATGTTACAGGACATCAAGCGTCAACCCAAGGTGGTTGAGCGCCTGCTTTCCTTGCCTCTGGAGTATTGGAGTCAGTTCATGATGGTGGAGCAAGAGAACATTGACCCCCTACATGTCATTGAAAACTCAAATGCCTTTTCAACACCACAGACACCAGATATTAAAGTGAGTTTACTGGGACCTGTGACCACTCCTGAACATCAGCTTCTCAAGACTCCTTCATCTAGTTCCCTGTCACAGAGAGTCCGTTCCACCCTCACCAAGAACACTCCTAGATTTGGGAGCAAAAGCAAGTCTGCCACTAACCTAGGACGACAAGGCAACTTTTTTGCTTCTCCAATGCTCAAGTGAAGTCACATCTGCCTGTTACTTCCCAGCATTGACTGACTATAAGAAAGGACACATCTGTACTCTGCTCTGCAGCCTCCTGTACTCATTACTACTTTTAGCATTCTCCAGGCTTTTACTCAAGTTTAATTGTGCATGAGGGTTTTATTAAAACTATATATATCTCCCCTTCCTTCTCCTCAAGTCACATAATATCAGCACTTTGTGCTGGTCATTGTTGGGAGCTTTTAGATGAGACATCTTTCCAGGGGTAGAAGGGTTAGTATGGAATTGGTTGTGATTCTTTTTGGGGAAGGGGGTTATTGTTCCTTTGGCTTAAAGCCAAATGCTGCTCATAGAATGATCTTTCTCTAGTTTCATTTAGAACTGATTTCCGTGAGACAATGACAGAAACCCTACCTATCTGATAAGATTAGCTTGTCTCAGGGTGGGAAGTGGGAGGGCAGGGCAAAGAAAGGATTAGACCAGAGGATTTAGGATGCCTCCTTCTAAGAACCAGAAGTTCTCATTCCCCATTATGAACTGAGCTATAATATGGAGCTTTCATAAAAATGGGATGCATTGAGGACAGAACTAGTGATGGGAGTATGCGTAGCTTTGATTTGGATGATTAGGTCTTTAATAGTGTTGAGTGGCACAACCTTGTAAATGTGAAAGTACAACTCGTATTTATCTCTGATGTGCCGCTGGCTGAACTTTGGGTTCATTTGGGGTCAAAGCCAGTTTTTCTTTTAAAATTGAATTCATTCTGATGCTTGGCCCCCATACCCCCAACCTTGTCCAGTGGAGCCCAACTTCTAAAGGTCAATATATCATCCTTTGGCATCCCAACTAACAATAAAGAGTAGGCTATAAGGGAAGATTGTCAATATTTTGTGGTAAGAAAAGCTACAGTCATTTTTTCTTTGCACTTTGGATGCTGAAATTTTTCCCATGGAACATAGCCACATCTAGATAGATGTGAGCTTTTTCTTCTGTTAAAATTATTCTTAATGTCTGTAAAAACGATTTTCTTCTGTAGAATGTTTGACTTCGTATTGACCCTTATCTGTAAAACACCTATTTGGGATAATATTTGGAAAAAAAGTAAATAGCTTTTTCAAAATGAAAAAAAAAA SEQ.ID NO. 44 SEQ.ID NO. 87AGGCGCTAGAGGCGGGGGCGCCGGGAGGCGCGGGCTTTGCTCCTGGGGTCTCGGCCTTGGCCGGCTGMTDLNDNICKRYIKMITNIVILSLIIGACCTGACCCTAGGGCGGCTTGCGCAGCTGTCGGGACGTGACTGCGTTCAGCCGCGTCGGGCGTGCTCISLAFWIISMTASTYYGNLRPISPWTCCCAGACTTGCCCAAGTTCGGGTGCCCTAGCTGCCCCTTTGCAGCCGCTGGCCTACCCGGCCCGCGRWLFSVVVPVLIVSNGLKKKSLDHSGGGTGAGAAGGTTGCGACGGGAGGTGGGTGGAACTCGCCAGCGCCGGGACCGCGGATTGGCTGCCTCGALGGLVVGFILTIANFSFFTSLLMFFGCTTTCTCTTTTCCCCGTGGGCTCCGGCGTGAGGCGCTGAAGCGGCCGGCAGCCGGCGACCGGCCCTLSSSKLTKWKGEVKKRLDSEYKEGGQCACCGTCCGCCGGGTTGCGCTCTGCTTTTGCGGTGAGGCGTTGACCACGCCCATATGAATTGGAGCTRNWVQVFCNGAVPTELALLYMIENGPCTCCGCCAGTAGGAGTTTCCGGAAGGAGTTTGAATTTTTGTGATTTTTATGCTTGTTTGGTCGGTGGGEIPVDFSKQYSASWMCLSLLAALACAATATGTTGGGATTTATGTTTGCCTCTGAACAAGTGTCTTGCTCACATCGTAAATGACTTTCTCTCCSAGDTWASEVGPVLSKSSPRLITTWEGAAACGCTAAATATTCTTTCCCGCAGGAGCTCATATCCTTATTTTCCATGACAGATCTTAACGACAAKVPVGTNGGVTVVGLVSSLLGGTFVGTATATGCAAAAGATATATAAAGATGATAACTAATATAGTTATACTGAGCCTGATCATTTGCATTTCGIAYFLTQLIFVNDLDISAPQWPIIAFTTAGCTTTCTGGATTATATCAATGACTGCAAGCACCTATTATGGTAACTTACGACCTATTTCTCCGTGGLAGLLGSIVDSYLGATMQYTGLDEGGCGTTGGCTGTTTTCTGTTGTTGTTCCTGTTCTGATCGTCTCTAATGGCCTTAAAAAGAAAAGTCTSTGMVVNSPTNKARHIAGKPILDNNAAGATCACAGTGGGGCTCTAGGAGGGCTAGTCGTTGGATTTATCCTAACCATTGCAAATTTCAGCTTTVNLFSSVLIALLLPTAAWGFWPRGTTTACCTCTTTGCTGATGTTTTTCTTGTCTTCTTCGAAACTCACTAAATGGAAGGGAGAAGTGAAGAAGCGTCTAGATTCAGAATATAAGGAAGGTGGGCAAAGGAATTGGGTTCAGGTGTTCTGTAATGGAGCTGTACCCACAGAACTGGCCCTGCTGTACATGATAGAAAATGGCCCCGGGGAAATCCCAGTCGATTTTTCCAAGCAGTACTCCGCTTCCTGGATGTGTTTGTCTCTCTTGGCTGCACTGGCCTGCTCTGCTGGAGACACATGGGCTTCAGAAGTTGGCCCAGTTCTGAGTAAAAGTTCTCCAAGACTGATAACAACCTGGGAGAAAGTTCCAGTTGGTACCAATGGAGGAGTTACAGTGGTGGGCCTTGTCTCCAGTCTCCTTGGTGGTACCTTTGTGGGCATTGCATACTTCCTCACACAGCTGATTTTTGTGAATGATTTAGACATTTCTGCCCCGCAGTGGCCAATTATTGCATTTGGTGGTTTAGCTGGATTACTAGGATCAATTGTGGACTCATACTTAGGGGCTACAATGCAGTATACTGGGTTGGATGAAAGCACTGGCATGGTGGTCAACAGCCCAACAAATAAGGCAAGGCACATAGCAGGGAAACCCATTCTTGATAACAACGCAGTGAATCTGTTTTCTTCTGTTCTTATTGCCCTCTTGCTCCCAACTGCTGCTTGGGGTTTTTGGCCCAGGGGGTGAACTTTATTTCATTTCCACAGGTTGAAACTGGTGAGTCCAGCTAAATTTGCAATTCCAACTTTCATCCTAAGAATAATAACTGTAATGGCAAAGCGGAAATGCCAGTTCCTCCTGTATTCCATTGAGATGGGATTTCACATTTTCCTCTCATCAACTCCCCTGTAATAGCTAGCGTCTTTCTAGTGAAAGAGAAGAATTCCTAGAACTTATGCATTTTTTTCCTGCTGAATGGAAGTCTTGAGCAATGAAGCTATATTGTCCCTACATATTACTATATATTGAACTGAAAGTTCTTACATAATCAATGTCAAGTTTTGTCTTATTTTGTTTTGTTTGTTTAAACCAGTGTAGGAAATAAAAGTGATGATATTTAAAATAGTTCTCAGTTGAAGCAGAGAAATGCCACTGTGCTAGTTGCCCAAATGTTGTATCTATTTTAAATAGTTTAAGCTGATGTGTATGGGAGCCTAAACAAGTGTAGTATCCTGAACTTCTCCCATTAATTGCTATTCACAATTGGGAAAAGTGTGGAGATTGGTTCCTAGTGAGTTTTGTGGCCTACTCCACATTTGTTCTTCCTTCCTCAGGGTTAGTGATGAAAAAAAGTAAATATCTTTTTCATATGTCCATTAGAATGTATGAAAAAAATCATTTTAACTAAAAGCAAAAGAATTTTATCTTATATCTAAAAAATATATAACTTACTATATGTTTCAGTTGCTCTCTGAACAAAAATTATCTTCAATTTAATATGTGGAATGTGTTTTCTAGCTTTCTTTGAATTATGTATGGCAACCTGGTTTAGCACTGGCATCCTGAACAGTTAAGAGTCACTGGGAAATTATTGTATTTCTTTATAAATTTACTGTCATATCAATTGCTGGAAAATGCTATGATTTTTCTATTATTACCTTCTAAGTTGTATTCTCTCTTACACTGTAGCCTCAACTAAGGCAATTCTGCTATGTTTGTTCTTCACTATGATTTACTGTGTGCCAAAGGAGTTTTGACAGGGTACAGAGTATTTTACTAAAAGTATTTTTAAATGTTTCTCATGTGATTTCTGTACCTTCTTCCTCCTGCCCCTTTTGCTTTTTTAAAGAAACTGGGGAAGGATTTATGAATACACCACCACCAGAGTGGATAATGCTTAGAATTCTTTATTGGTGGCCCTACTATGGTGATGATCTAGAACTGACTTACTTCAGGACAGAAGAAAAAACAATCACACCCTTAACCTTTAAGCCAGTTAGATCAGGGGGTTGCAACAATTGGGTTAAACTTTGGGTATACATTGGAAGCACCAGGGCATGTTTGCTTTTTTTGTTTATGTGTTTGTTTTTTGAGACAGAGTCTCACACTGTGGCCCAGGCTGGACTCCAGCACAGTGGCATGATCTCAGCTCCGCCTCCTGGGTTCACGTGATTCTCATGCCTCAGCCTCCCAAGTAGCTGGGATCACAGGCGTGCACCATCACGCCCGGCTAATTTTTGTATTTTCAGTAGAGACAGGGTTTCGCCACGTTGGCTAGGCTGGTCTCGAACTCCTGACCTCAAGTGATCTGCCCATCTCAGCCTCCCAAAGATCTATTACAAGATGTGAGCCACTGTGCCCAGCCACCAGGGCATGTTTTTAAAAAAGTACTGATGTCTGGGTTTCACACTGCAAAATTCTGATTTATCTGATCTAAGGTACAGCCTGGATATTGAGACTTTTTAAAGCTCTGACTGTACATTGAATCATCATGTAAGGAGTTTTTAAAACATTGTTGCCAGGGCCCCTTTCTAGACCAAGTTAGTCAGAATGTTGGACAATGAGGCCCATGCATGGGTATTTTTACAAAGCTCTCTGGGAGATTCTAATGCTTAACCAAATTGAGAAGCACTGAATAAGAATATCCTGGGCCGGGCGCACTGGCTCATGCCTGTAATCCCAGCATTTTGGAAGGCCGAGGCGGGTGGATCACTTGAGGTCAGGAGTTCGAGACCAGCCTGGCCAACATGGTGAAACACCGTCTCTACTAAAAATACAAAAAATTAGGTGTGGTGGTGCGTGCCTGTATTCCCAGCCACTCAGGAGGCTGAGGCAGGAGAATCGCTGGAACCTGGGATGTGGAGGTTGCAGTGAGCCAAGATTGCACCACTGTACTCCAGCCTGGGCAACAGAGGGAGACTCCATCTAGACTCCATCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGAATATTCTAAGCACTAGAACTACATAAGAATGTCCTAAAGCACTGTATCTAAGCACTTGAAAAGAATGGGACTTTTCGGTTTTAGGGAGATAACTATTAGCAACCACACAATATGTTATCTTTATGGATGAATAACTTCTGGTAATGACACAGTGTCTTACAGCTACATCATTTATAAAATCATGTGTCAGTTTTCACACAGCCTGCACATCGTTCTGACATGCCCTTTTTTTCCCTGGAGATTTATCCTCATGACATACAAGGGGACAAAAATATTTATTGGGACTGTCTTTGAATTTAGTAGAATCACTGTATCATTAACAGTTTGGGGAAGTACTGCTTTGCAGTCCTTTATTTGAAAACTTAGGTCTAGCTGTGTTTTGCATCAAAATTTTTGAGCTATTCAAAAACTAATAGGATCTGTGTAAAATATTTCACTCAAAACTACTAAAAAAAAGTCTGGGATGGCAGCTCATTATCAAATATACTCCTATTTTTGTGGTGATTTATGAACATCCCCACTAAGTATAACTAAAGATCATAAAGAGCCTCAGATCAAGTTTGGTCAGGTTTTGTCACCAAGCTTTGTAAATAAACTGGTTTTCATAGCTTTTTGGAGATGAGAATTGAGGATAAGAAATTGTGTCTCTGTCCTTTTTTTTTTTTTTTGTTAAGTCTTACATGTATTTTACTGTAACATCTTTTGAATTGGATATTTAACTAATTCAACATATTTTTCCTCTTTGCAGAATGGGCAGTTCATGTTAAAATCACTTTTCATGGAAAGAGCTCTATGTAACAGCATAATAAAACTGCCTACCTAGCAGCATAAA SEQ.ID NO. 45 STAR clone:CNGGACACATCAAACTGCTTATCCAGGNACCACTAGAAGTGAATCTCTTCTTGAGTATTCCATACTGCTGCCCCTGCTATTCACTTGGGGTCCCAGTCAGTTGTTACTATATATTTGTCATCTATTGTGAGAGTCGTGATATCACCTTCCACATCAGTGATACTGAGAAGGAACAAATCTGCCAAAGATGCTTCACAGTTAGTTGTTACCTTTTTAAGAAGACTGTGCTTGAAAATTATGGTAAAACACATTTAGAAGAAGGATGTGCATTTTCACATCAGTCTATGAAGTATAACTTGACATTTAAATTAAAATGCTGTTCTTCAAAATCGASEQ.ID NO. 46 STAR clone:GTTCCCGACTAGCTGCCCNTGCACATTATCTTCATTTTCCTGGAATTTGATACAGAGAGCAATTTATAGCCNATTGATAGCTTATGCTGTTTCAATGTAAATTCGTGGTAAATAACTTAGGAACTGCCTCTTCTTTTTCTTTGAAAACCTACTTATAACTGTTGCTAATAAGAATGTGTATTGTTCAGGACAACTTGTCTCCATACAGTTGGGTTGTAACCCTCATGCTTGGCCCAAATAAACTCTCTACTTATATCAGTASEQ.ID NO. 47 STAR clone:CTAGGGGTCCTGACGGTTCTCTGGCTCCAAGTCTGGCCCCTCAACCTCCCTGGTCATCAGTGGGCTCCAGGCTGAGGATGAGGCTGATTACTACTGTGCAGCATGGGATGACAGCCTGAAAGGTCCTGCGTTCGGAGGAGGCACCCACCTGACCGTCCTCGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCACACTGGTGTGTCTCGTAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCAAGGTGGGAGTGGAGACCACCAAACCCTCCAAACAAAGCAACAACAAGTATGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCGGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTGCAGAATGCTCTTAGGCCCCCGACCCTCACCCCACCCACAGGGGCCTGGAGCTGCAGGTTCCCAGGGGAGGGGTCTCTGCCCCCATCCCAAGTCATCCAGCCCTTCTCAATAAATATCCTCATCGTCAACGASEQ.ID NO. 48 SEQ.ID NO. 88GGTAGTTGGTTGTGGGCACTGGGTTAGAGGTATCACGTGGGGGCACTTTCGTCTTAGCTTTTGGACAMAQSRDGGNPFAEPSELDNPFQDPAVAGACGCAGGCGCAACCCACGGCTGCTGCGGGGATCCTTGTGGCCCTTCCGGTCGGTGGAACCAATCCIQHRPSRQYATLDVYNPFETREPPPAGTGCACAGAGAAGCGGGGCGAACTGAGGCGAGTGAAGTGGACTCTGAGGGCTACCGCTACCGCCACTYEPPAPAPLPPPSAPSLQPSRKLSPTGCTGCGGCAGGGGCGTGGAGGGCAGAGGGCCGCGGAGGCCGCAGTTGCAAACATGGCTCAGAGCAGAEPKNYGSYSTQASAAAATAELLKKQEGACGGCGGAAACCCGTTCGCCGAGCCCAGCGAGCTTGACAACCCCTTTCAGGACCCAGCTGTGATCCELNRKAEELDRRERELQHAALGGTATAGCACCGACCCAGCCGGCAGTATGCCACGCTTGACGTCTACAACCCTTTTGAGACCCGGGAGCCACCRQNNWPPLPSFCPVQPCFFQDISMEIACCAGCCTATGAGCCTCCAGCCCCTGCCCCATTGCCTCCACCCTCAGCTCCCTCCTTGCAGCCCTCGPQEFQKTVSTMYYLWMCSTLALLLNFAGAAAGCTCAGCCCCACAGAACCTAAGAACTATGGCTCATACAGCACTCAGGCCTCAGCTGCAGCAGLACLASFCVETNNGAGFGLSILWVLLCCACAGCTGAGCTGCTGAAGAAACAGGAGGAGCTCAACCGGAAGGCAGAGGAGTTGGACCGAAGGGAFTPCSFVCWYRPMYKAFRSDSSFNFFGCGAGAGCTGCAGCATGCTGCCCTGGGGGGCACAGCTACTCGACAGAACAATTGGCCCCCTCTACCTVFFFIFFVQDVLFVLQAIGIPGWGFSTCTTTTTGTCCAGTTCAGCCCTGCTTTTTCCAGGACATCTCCATGGAGATCCCCCAAGAATTTCAGAGWISALVVPKGNTAVSVLMLLVALLFAGACTGTATCCACCATGTACTACCTCTGGATGTGCAGCACGCTGGCTCTTCTCCTGAACTTCCTCGCTGIAVLGIVMLKRIHSLYRRTGASFQCTGCCTGGCCAGCTTCTGTGTGGAAACCAACAATGGCGCAGGCTTTGGGCTTTCTATCCTCTGGGTCKAQQEFAAGVFSNPAVRTAAANAAAGCTCCTTTTCACTCCCTGCTCCTTTGTCTGCTGGTACCGCCCCATGTATAAGGCTTTCCGGAGTGACAAAENAFRAPGTTCATTCAATTTCTTCGTTTTCTTCTTCATTTTCTTCGTCCAGGATGTGCTCTTTGTCCTCCAGGCCATTGGTATCCCAGGTTGGGGATTCAGTGGCTGGATCTCTGCTCTGGTGGTGCCGAAGGGCAACACAGCAGTATCCGTGCTCATGCTGCTGGTCGCCCTGCTCTTCACTGGCATTGCTGTGCTAGGAATTGTCATGCTGAAACGGATCCACTCCTTATACCGCCGCACAGGTGCCAGCTTTCAGAAGGCCCAGCAAGAATTTGCTGCTGGTGTCTTCTCCAACCCTGCGGTGCGAACCGCAGCTGCCAATGCAGCCGCTGGGGCTGCTGAAAATGCCTTCCGGGCCCCGTGACCCCTGACTGGGATGCCCTGGCCCTGCTACTTGAGGGAGCTGACTTAGCTCCCGTCCCTAAGGTCTCTGGGACTTGGAGAGACATCACTAACTGATGGCTCCTCCGTAGTGCTCCCAATCCTATGGCCATGACTGCTGAACCTGACAGGCGTGTGGGGAGTTCACTGTGACCTAGTCCCCCCATCAGGCCACACTGCTGCCACCTCTCACACGCCCCAACCCAGCTTCCCTCTGCTGTGCCACGGCTGTTGCTTCGGTTATTTAAATAAAAAGAAAGTGGAACTGGAACTGACAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 49 STAR clone:CTGCAAGAACTANTCATTCNAGGTCACCAGANAGGAGCCCTGACCCNTCGCTGCCCAGCCTGTCCTTGTGTCGTCTTTTTACGGGAGACGACTGGATCATGGGGGCGGATTTTCCCCTTGCTGTTCTCATGATAGTGAGTTCTCATGAGATCTGGTTGTTTAAAAGTGTATAGCACTTCCTGCTTCACTCTCTCCCACTCCACCATGTGAAGAAGGTGCCTTTGCCCTTCCGCCACGACTGTGTTTCCTGAGGCCTCCCCAGCCATGCTTCCTGTACAGCCTGCAGAACTGTGAGTTAATTAAACCTCTTTTCTTCATAAAGAACA SEQ.ID NO. 50SEQ.ID NO. 89TCAAGATTAAACGACAAGGACAGACATGGCTCAGCGGATGACAACACAGCTGCTGCTCCTTCTAGTGMAQRMTTQLLLLLVWVAVVGEAQTRITGGGTGGCTGTAGTAGGGGAGGCTCAGACAAGGATTGCATGGGCCAGGACTGAGCTTCTCAATGTCTAWARTELLNVCMNAKHHKEKPGPEDKGCATGAACGCCAAGCACCACAAGGAAAAGCCAGGCCCCGAGGACAAGTTGCATGAGCAGTGTCGACCLHEQCRPWRKNACCSTNTSQEAHKDVCTGGAGGAAGAATGCCTGCTGTTCTACCAACACCAGCCAGGAAGCCCATAAGGATGTTTCCTACCTASYLYRFNWNHCGEMAPACKRHFIQDTTATAGATTCAACTGGAACCACTGTGGAGAGATGGCACCTGCCTGCAAACGGCATTTCATCCAGGACACLYECSPNLGPWIQQVDQSWRKERVLCCTGCCTCTACGAGTGCTCCCCCAACTTGGGGCCCTGGATCCAGCAGGTGGATCAGAGCTGGCGCAANVPLCKEDCEQWWEDCRTSYTCKSNWAGAGCGGGTACTGAACGTGCCCCTGTGCAAAGAGGACTGTGAGCAATGGTGGGAAGATTGTCGCACCHKGWNWTSGFNKCAVGAACQPFHFYFTCCTACACCTGCAAGAGCAACTGGCACAAGGGCTGGAACTGGACTTCAGGGTTTAACAAGTGCGCAGPTPTVLCNEIWTHSYKVSNYSRGSGRTGGGAGCTGCCTGCCAACCTTTCCATTTCTACTTCCCCACACCCACTGTTCTGTGCAATGAAATCTGCIQMWFDPAQGNPNEEVARFYAAAMSGACTCACTCCTACAAGGTCAGCAACTACAGCCGAGGGAGTGGCCGCTGCATCCAGATGTGGTTCGACGAGPWAAWPFLLSLALMLLWLLSCCAGCCCAGGGCAACCCCAATGAGGAGGTGGCGAGGTTCTATGCTGCAGCCATGAGTGGGGCTGGGCCCTGGGCAGCCTGGCCTTTCCTGCTTAGCCTGGCCCTAATGCTGCTGTGGCTGCTCAGCTGACCTCCTTTTACCTTCTGATACCTGGAAATCCCTGCCCTGTTCAGCCCCACAGCTCCCAACTATTTGGTTCCTGCTCCATGGTCGGGCCTCTGACAGCCACTTTGAATAAACCAGACACCGCACATGTGTCTTGAGAATTATTTGG SEQ.ID NO. 90 biotin-actgtactAACCCTGCGGCCGCTTTTTTTTTTTTTTTTTTTTVSEQ.ID NO. 91 GGAATTCTAATACGACTCACTATAGGGAGACGAAGACAGTAGACAGGSEQ.ID NO. 92 CGCGCCTGTCTACTGTCTTCGTCTCCCTATAGTGAGTCGTATTAGAATTCSEQ.ID NO. 93 GGAATTCTAATACGACTCACTATAGGGAGAGCCTGCACCAACAGTTAACAGGSEQ.ID NO. 94 CGCGCCTGTTAACTGTTGGTGCAGGCTCTCCCTATAGTGAGTCGTATTAGAATTCSEQ.ID NO. 95 GGGAGACGAAGACAGTAGA SEQ.ID NO. 96 GCCTGCACCAACAGTTAACASEQ.ID NO. 97 GGAATTCTAATACGACTCACTATAGGGA SEQ.ID NO. 98CGCGTCCCTATAGTGAGTCGTATTAGAATTC SEQ.ID NO. 99TTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTCTAATACGACTCACTATAGGGAGATGGAGAAAAAAATCACTGGACGCGTGGCGCGCCATTAATTAATGCGGCCGCTAGCTCGAGTGATAATAAGCGGATGAATGGCTGCAGGCATGCAAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCAATGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGG SEQ.ID NO. 100TTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTCAATTAACCCTCACTAAAGGGAGACTTGTTCCAAATGTGTTAGGcgCGCCGCATGCGTCGACGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTTATTGTGCTGTCTCATCATTTTGGCAAAGAATTCACTCCTCAGGTGCAGGCTGCCTATCAGAAGGTGGTGGCTGGTGTGGCCAATGCCCTGGCTCACAAATACCACTGAGATCTTTTTCCCTCTGCCAAAAATTATGGGGACATCATGAAGCCCCTTGAGCATCTGACTTCTGGCTAATAAAGGAAATTTATTTTCATTGCAAAAAAAAAAAGCGGCCGCTCTTCTATAGTGTCACCTAAATGGCCCAGCGGCCGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCAAAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGG SEQ.ID NO. 101TCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGCCAAGCTTTTCCAAAAAACTACCGTTGTTATAGGTGTCTCTTGAACACCTATAACAACGGTAGTGGATCCCGCGTCCTTTCCACAAGATATATAAACCCAAGAAATCGAAATACTTTCAAGTTACGGTAAGCATATGATAGTCCATTTTAAAACATAATTTTAAAACTGCAAACTACCCAAGAAATTATTACTTTCTACGTCACGTATTTTGTACTAATATCTTTGTGTTTACAGTCAAATTAATTCTAATTATCTCTCTAACAGCCTTGTATCGTATATGCAAATATGAAGGAATCATGGGAAATAGGCCCTCTTCCTGCCCGACCTTGGCGCGCGCTCGGCGCGCGGTCACGCTCCGTCACGTGGTGCGTTTTGCCTGCGCGTCTTTCCACTGGGGAATTCATGCTTCTCCTCCCTTTAGTGAGGGTAATTCTCTCTCTCTCCCTATAGTGAGTCGTATTAATTCCTTCTCTTCTATAGTGTCACCTAAATCGTTGCAATTCGTAATCATGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAAAAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTATTGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTAGCTTGCATGCCTGCAGGTCGGCCGCCACGACCGGTGCCGCCACCATCCCCTGACCCACGCCCCTGACCCCTCACAAGGAGACGACCTTCCATGACCGAGTACAAGCCCACGGTGCGCCTCGCCACCCGCGACGACGTCCCCCGGGCCGTACGCACCCTCGCCGCCGCGTTCGCCGACTACCCCGCCACGCGCCACACCGTCGACCCGGACCGCCACATCGAGCGGGTCACCGAGCTGCAAGAACTCTTCCTCACGCGCGTCGGGCTCGACATCGGCAAGGTGTGGGTCGCGGACGACGGCGCCGCGGTGGCGGTCTGGACCACGCCGGAGAGCGTCGAAGCGGGGGCGGTGTTCGCCGAGATCGGCCCGCGCATGGCCGAGTTGAGCGGTTCCCGGCTGGCCGCGCAGCAACAGATGGAAGGCCTCCTGGCGCCGCACCGGCCCAAGGAGCCCGCGTGGTTCCTGGCCACCGTCGGCGTCTCGCCCGACCACCAGGGCAAGGGTCTGGGCAGCGCCGTCGTGCTCCCCGGAGTGGAGGCGGCCGAGCGCGCCGGGGTGCCCGCCTTCCTGGAGACCTCCGCGCCCCGCAACCTCCCCTTCTACGAGCGGCTCGGCTTCACCGTCACCGCCGACGTCGAGGTGCCCGAAGGACCGCGCACCTGGTGCATGACCCGCAAGCCCGGTGCCTGACGCCCGCCCCACGACCCGCAGCGCCCGACCGAAAGGAGCGCACGACCCCATGGCTCCGACCGAAGCCACCCGGGGCGGCCCCGCCGACCCCGCACCCGCCCCCGAGGCCCACCGACTCTAGAGGATCATAATCAGCCATACCACATTTGTAGAGGTTTTACTTGCTTTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAAAATGAATGCAATTGTTGTTGTTAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCAATCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTC SEQ.ID NO. 102Sequence information not disclosed by Ambion SEQ.ID NO. 103GTCAAGAAACCACACTTTA SEQ.ID NO. 104 GTGACATGGAACCCAGCGA SEQ.ID NO. 105ACCGTGGCTGCTCGATAAA SEQ.ID NO. 106 GCCAGAGAGCACAGAAATA SEQ.ID NO. 107GAGGAATGCCTCTAAGAAA SEQ.ID NO. 108 GGGAACGAGAAGGGCTTCT SEQ.ID NO. 109AGCTGGAGGAATGAGAATT SEQ.ID NO. 110 AGGGCCAAAGCTTTCCATA SEQ.ID NO. 111GGCAGGCTGTCCGCTTAAA SEQ.ID NO. 112 GGTCCTTAGGCACCCAGAT SEQ.ID NO. 113GCGGAGCCCAGGGAGAATA SEQ.ID NO. 114 GCCCGGATTGATGACATAT SEQ.ID NO. 115GTGGAGGCTGAGTTTCCAT SEQ.ID NO. 116 GGATGTTAACCTGCGAAAT SEQ.ID NO. 117GGTCAGCAGGGTTCATTTA SEQ.ID NO. 118 GCCTCAGGAACAAGATGAA SEQ.ID NO. 119GCGCGAGATCCTCTCCATT SEQ.ID NO. 120 GCGCCAGAGGAGCGGGAAG SEQ.ID NO. 121GCCGCCCAGTTCAATACAA SEQ.ID NO. 122 GAGCTTACAACCTGCCTTA SEQ.ID NO. 123GGCGCCCACTACCCAAGAA SEQ.ID NO. 124 GAGTCAGGGATGGGTCCAT SEQ.ID NO. 125GGGCCAGTCTGTACTCATT SEQ.ID NO. 126 GGGAATTCCATCTCCATAT SEQ.ID NO. 127GGCGCAGATCACCCAGAAG SEQ.ID NO. 128 GAGCATCCTGGTGAGGAAT SEQ.ID NO. 129GGTGCCACATGACTAGGAT SEQ.ID NO. 130 GCTGCAGACGTGTATGCAT SEQ.ID NO. 131GCGGAGGCACTGGGCTTAT SEQ.ID NO. 132 GCCCGCTTACTTCCTGGAG SEQ.ID NO. 133GCTCTGCTCAAGTTGGATA SEQ.ID NO. 134 GCTGCTGCCTTGCAGTTTG SEQ.ID NO. 135GCCCTTACCTGATGCTAAA SEQ.ID NO. 136 GGCACCTACAAATGTTATA SEQ.ID NO. 137GAGGCCTGGAAGCTCCTAA SEQ.ID NO. 138 GCAGCTTCAGGAGGTTAAA SEQ.ID NO. 139GCCGGACCTCTTCATCTTA SEQ.ID NO. 140 GCGTCCATCACGGAAACAT SEQ.ID NO. 141GTCATCAGGACGTCCATTA SEQ.ID NO. 142 GACACGATCTACCCTCAAA SEQ.ID NO. 143GGGCCATAGGGAAGCTTGA SEQ.ID NO. 144 GCCCACGTGTTGAGATCAA SEQ.ID NO. 145GCTCCCACTGATTCCACAT SEQ.ID NO. 146 GCCAGAGAGTAAAAGGGAT SEQ.ID NO. 147GGCATATGGAAGGAGCATT SEQ.ID NO. 148 GTGGTTTGGTTCAGCAGTT SEQ.ID NO. 149GGCCTCCAGCCACGTAATT SEQ.ID NO. 150 GGCGCTGCTGCCGCTCATC SEQ.ID NO. 151GGGCTGGAACTGGACTTCA SEQ.ID NO. 152 GCCCATAAGGATGTTTCCT SEQ.ID NO. 153GCGTCCGGGCCTGTCTTCAACCT SEQ.ID NO. 154 GCCCCACCCTCTACCCCACCACTASEQ.ID NO. 155 GAGATCCTGATCAAGGTGCAGG SEQ.ID NO. 156TGCACGCTCACAGCAGTCAGG SEQ.ID NO. 157 AACATGACTAAGATGCCCAACCSEQ.ID NO. 158 AATCTCCTTCACCTCCACTACTG SEQ.ID NO. 159AAGCATAGCCATAGGTGATTGG SEQ.ID NO. 160 ACAGGTATCAGACAAGGGAGCAGSEQ.ID NO. 161 TTACGACCTATTTCTCCGTGG SEQ.ID NO. 162AATGCAATAATTGGCCACTGC SEQ.ID NO. 163 ACACATCAAACTGCTTATCCAGGSEQ.ID NO. 164 ACTGATGTGAAAATGCACATCC SEQ.ID NO. 165ATGGCTCATACAGCACTCAGG SEQ.ID NO. 166 GAACTGTCACTCCGGAAAGCCTSEQ.ID NO. 167 TGAAGGTCGGAGTCAACGGATTTGGT SEQ.ID NO. 168CATGTGGGCCATGAGGTCCACCAC SEQ.ID NO. 169 SEQ.ID NO. 170ccctaatgcctccaacaataactgttgactttttattttcagtcagagaagcctggcaaccaagaacMKILILGIFLFLCSTPAWAKEKHYYItgtttttttggtggtttacgagaacttaactgaattggaaaatatttgctttaatgaaacaatttacGIIETTWDYASDHGEKKLISVDTEHStcttgtgcaacactaaattgtgtcaatcaagcaaataaggaagaaagtcttatttataaaattgcctNIYLQNGPDRIGRLYKKALYLQYTDEgctcctgattttacttcatttcttctcaggctccaagaaggggaaaaaaatgaagattttgatacttTFRTTIEKPVWLGFLGPIIKAETGDKggtatttttctgtttttatgtagtaccccagcctgggcgaaagaaaagcattattacattggaattaVYVHLKNLASRPYTFHSHGITYYKEHttgaaacgacttgggattatgcctctgaccatggggaaaagaaacttatttctgttgacacggaacaEGAIYPDNTTDFQRADDKVYPGEQYTttccaatatctatcttcaaaatggcccagatagaattgggagactatataagaaggccctttatcttYMLLATEEQSPGEGDGNCVTRIYHSHcagtacacagatgaaacctttaggacaactatagaaaaaccggtctggcttgggtttttaggccctaIDAPKDIASGLIGPLIICKKDSLDKEttatcaaagctgaaactggagataaagtttatgtacacttaaaaaaccttgcctctaggccctacacKEKHIDREFVVMFSVVDENFSWYLEDctttcattcacatggaataacttactataaggaacatgagggggccatctaccctgataacaccacaNIKTYCSEPEKVDKDNEDFQESNRMYgattttcaaagagcagatgacaaagtatatccaggagagcagtatacatacatgttgcttgccactgSVNGYTFGSLPGLSMCAEDRVKWYLFaagaacaaagtcctggggaaggagatggcaattgtgtgactaggatttaccattcccacattgatgcGMGNEVDVHAAFFHGQALTNKNYRIDtccaaaagatattgcctcaggactcatcggacctttaataatctgtaaaaaagattctctagataaaTINLFPATLFDAYMVAQNPGEWMLSCgaaaaagaaaaacatattgaccgagaatttgtggtgatgttttctgtggtggatgaaaatttcagctQNLNHLKAGLQAFFQVQECNKSSSKDggtacctagaagacaacattaaaacctactgctcagaaccagagaaagttgacaaagacaacgaagaNIRGKHVRHYYIAAEEIIWNYAPSGIcttccaggagagtaacagaatgtattctgtgaatggatacacttttggaagtctcccaggactctccDIFTKENLTAPGSDSAVFFEQGTTRIatgtgtgctgaagacagagtaaaatggtacctttttggtatgggtaatgaagttgatgtgcacgcagGGSYKKLVYREYTDASFTNRKERGPEctttctttcacgggcaagcactgactaacaagaactaccgtattgacacaatcaacctctttcctgcEEHLGILGPVIWAEVGDTIRVTFHNKtaccctgtttgatgcttatatggtggcccagaaccctggagaatggatgctcagctgtcagaatctaGAYPLSIEPIGVRFNKNNEGTYYSPNaaccatctgaaagccggtttgcaagcctttttccaggtccaggagtgtaacaagtcttcatcaaaggYNPQSRSVPPSASHVAPTETFTYEWTataatatccgtgggaagcatgttagacactactacattgccgctgaggaaatcatctggaactatgcVPKEVGPTNADPVCLAKMYYSAVDPTtccctctggtatagacatcttcactaaagaaaacttaacagcacctggaagtgactcagcggtgtttKDIFTGLIGPMKICKKGSLHANGRQKtttgaacaaggtaccacaagaattggaggctcttataaaaagctggtttatcgtgagtacacagatgDVDKEFYLFPTVFDENESLLLEDNIRcctccttcacaaatcgaaaggagagaggccctgaagaagagcatcttggcatcctgggtcctgtcatMFTTAPDQVDKEDEDFQESNKMHSMNttgggcagaggtgggagacaccatcagagtaaccttccataacaaaggagcatatcccctcagtattGFMYGNQPGLTMCKGDSVVWYLFSAGgagccgattggggtgagattcaataagaacaacgagggcacatactattccccaaattacaacccccNEADVHGIYFSGNTYLWRGERRDTANagagcagaagtgtgcctccttcagcctcccatgtggcacccacagaaacattcacctatgaatggacLFPQTSLTLHMWPDTEGTFNVECLTTtgtccccaaagaagtaggacccactaatgcagatcctgtgtgtctagctaagatgtattattctgctDHYTGGMKQKYTVNQCRRQSEDSTFYgtggatcccactaaagatatattcactgggcttattgggccaatgaaaatatgcaagaaaggaagttLGERTYYIAAVEVEWDYSPQREWEKEtacatgcaaatgggagacagaaagatgtagacaaggaattctatttgtttcctacagtatttgatgaLHHLQEQNVSNAFLDKGEFYIGSKYKgaatgagagtttactcctggaagataatattagaatgtttacaactgcacctgatcaggtggataagKVVYRQYTDSTFRVPVERKAEEEHLGgaagatgaagactttcaggaatctaataaaatgcactccatgaatggattcatgtatgggaatcagcILGPQLHADVGDKVKIIFKNMATRPYcgggtctcactatgtgcaaaggagattcggtcgtgtggtacttattcagcgccggaaatgaggccgaSIHAHGVQTESSTVTPTLPGETLTYVtgtacatggaatatacttttcaggaaacacatatctgtggagaggagaacggagagacacagcaaacWKIPERSGAGTEDSACIPWAYYSTVDctcttccctcaaacaagtcttacgctccacatgtggcctgacacagaggggacttttaatgttgaatQVKDLYSGLIGPLIVCRRPYLKVFNPgccttacaactgatcattacacaggcggcatgaagcaaaaatatactgtgaaccaatgcaggcggcaRRKLEFALLFLVFDENESWYLDDNIKgtctgaggattccaccttctacctgggagagaggacatactatatcgcagcagtggaggtggaatggTYSDHPEKVNKDDEEFIESNKMHAINgattattccccacaaagggagtgggaaaaggagctgcatcatttacaagagcagaatgtttcaaatgGRMFGNLQGLTMHVGDEVNWYLMGMGcatttttagataagggagagttttacataggctcaaagtacaagaaagttgtgtatcggcagtatacNEIDLHTVHFHGHSFQYKHRGVYSSDtgatagcacattccgtgttccagtggagagaaaagctgaagaagaacatctgggaattctaggtccaVFDIFPGTYQTLEMFPRTPGIWLLHCcaacttcatgcagatgttggagacaaagtcaaaattatctttaaaaacatggccacaaggccctactHVTDHIHAGMETTYTVLQNEDTKSGcaatacatgcccatggggtacaaacagagagttctacagttactccaacattaccaggtgaaactctcacttacgtatggaaaatcccagaaagatctggagctggaacagaggattctgcttgtattccatgggcttattattcaactgtggatcaagttaaggacctctacagtggattaattggccccctgattgtttgtcgaagaccttacttgaaagtattcaatcccagaaggaaactggaatttgcccttctgtttctagtttttgatgagaatgaatcttggtacttagatgacaacatcaaaacatactctgatcaccccgagaaagtaaacaaagatgatgaggaattcatagaaagcaataaaatgcatgctattaatggaagaatgtttggaaacctacaaggcctcacaatgcacgtgggagatgaagtcaactggtatctgatgggaatgggcaatgaaatagacttacacactgtacattttcacggccatagcttccaatacaagcacaggggagtttatagttctgatgtctttgacattttccctggaacataccaaaccctagaaatgtttccaagaacacctggaatttggttactccactgccatgtgaccgaccacattcatgctggaatggaaaccacttacaccgttctacaaaatgaagacaccaaatctggctgaatgaaataaattggtgataagtggaaaaaagagaaaaaccaatgattcataacaatgtatgtgaaagtgtaaaatagaatgttactttggaatgactataaacattaaaagaagactggaagcatacaactttgtacatttgtgggggaaaactattaattttttgcaaatggaaagatcaacagactatataatgatacatgactgacacttgtacactaggtaataaaactgattcatacagtctaatgatatcaccgctgttagggttttataaaactgcatttaaaaaaagatctatgaccagatattctcctgggtgctcctcaaaggaacactattaaggttcattgaaatgttttcaatcattgccttcccattgatccttctaacatgctgttgacatcacacctaatattcagagggaatgggcaaggtatgagggaaggaaataaaaaataaaataaataaaatagaatgacacaaatttgagttttgtgaacccctgaacagatggtcttaaggacgttatctggaactggagaaaagcagagttgagagacaattctatagattaaatcctggtaaggacaaacattgccattagaagaaaagcttcaaaatagacctgtggcagatgtcacatgagtagaatttctgcccagccttaactgcattcagaggataatatcaatgaactaaacttgaactaaaaattttttaaacaaaaagttataaatgaagacacatggttgtgaatacaatgatgtatttctttattttcacatacactctagctaaaagagcaagagtacacatcaacaaaaatggaaacaaggctttggctgaaaaaaacatgcatttgacaaatcatgttaatagctagacaagaagaaagttagctttgtaaacttctacttcatttgattcagagaaacagagcatgagttttcttaaaagtaacaagaaaaSEQ.ID NO. 171 GCTTAAAAGAGTCCTCCTGTGGC SEQ.ID NO. 172TGGACATTGTTCTTAAAGTGTGG SEQ.ID NO. 173 AGGTTTTATGGCCACCGTCAGSEQ.ID NO. 174 ATCCTATACCGCTCGGTTATGC SEQ.ID NO. 175GGGCGGCGGCTCTTTCCTCCTC SEQ.ID NO. 176 GCTAGCGGCCCCATACTCG SEQ.ID NO. 177ACACTGGATGCCCTGAATGACACA SEQ.ID NO. 178 GCTTTGGCCCTTTTTGCTAASEQ.ID NO. 179 CCCACTTCTGTCTTACTGCATC SEQ.ID NO. 180CATAGTACTCCAGGGCTTATTC SEQ.ID NO. 181 AACGATTGCCCGGATTGATGACASEQ.ID NO. 182 TACTTGAGGCTGGGGTGGGAGATG SEQ.ID NO. 183CACTACGCCAGGCACCCCCAAA SEQ.ID NO. 184 CGAGGCGCACGGCAGTCT SEQ.ID NO. 185ATCCGTTGCTGCAGCTCGTTCCTC SEQ.ID NO. 186 ACCCTGCTGACCTTCTTCCATTCCSEQ.ID NO. 187 TCGGAGGAGGGCTGGCTGGTGTTT SEQ.ID NO. 188CTTGGGCGTCTTGGAGCGGTTCTG SEQ.ID NO. 189 AGAGCCTATTGAAGATGAACAGSEQ.ID NO. 190 TGATTGCCCCGGATCCTCTTAGG SEQ.ID NO. 191GGACAAATACGACGACGAGG SEQ.ID NO. 192 GGTTTCTTGGGTAGTGGGC SEQ.ID NO. 193CCCCGGAGAAGGAAGAGCAGTA SEQ.ID NO. 194 CGAAAGCCGGCAGTTAGTTATTGASEQ.ID NO. 195 GGCGGGCAACGAATTCCAGGTGTC SEQ.ID NO. 196TCAGAGGTTCGTCGCATTTGTCCA SEQ.ID NO. 197 CAACAGTCATGATGTGTGGATGSEQ.ID NO. 198 ACTGCACCTTGTCCGTGTTGAC SEQ.ID NO. 199CCGGCTGGCTGCTTTGTTTA SEQ.ID NO. 200 ATGATCAGCAGGTTCGTTGGTAGGSEQ.ID NO. 201 ATGCCGGAAGTGAATGTGG SEQ.ID NO. 202 GGTGACTCCGCCTTTTGATSEQ.ID NO. 203 ACATTCGCTTCTCCATCTGG SEQ.ID NO. 204 TGTCACGGAAGGGAACCAGGSEQ.ID NO. 205 ACGCTGCCTCTGGGTCACTT SEQ.ID NO. 206TTGGCAAATCAATGGCTTGTAAT SEQ.ID NO. 207 ATGGCTTGGGTCATCAGGACSEQ.ID NO. 208 GTGTCACTGGGCGTAAGATACTG SEQ.ID NO. 209CACCAAATCAGCTGCTACTACTCC SEQ.ID NO. 210 GATAAACCCCAAAGCAGAAAGATTSEQ.ID NO. 211 CGAGATTCCGTGGGCGTAGG SEQ.ID NO. 212 TGAGTGGGAGCTTCGTAGGSEQ.ID NO. 213 TCAGAGTGGACGTTGGATTAC SEQ.ID NO. 214TGCTTGAAATGTAGGAGAACA SEQ.ID NO. 215 GAGGGGCATCAATCACACCGAGAASEQ.ID NO. 216 CCCCACCGCCCACCCATTTAGG SEQ.ID NO. 217GGGGGCACCAGAGGCAGTAA SEQ.ID NO. 218 GGTTGTGGCGGGGGCAGTTGTGSEQ.ID NO. 219 ACAGACTCCTGTACTGCAAACC SEQ.ID NO. 220TACCGGTTCGTCCTCTTCCTC SEQ.ID NO. 221 GAAGTTCCTCACGCCCTGCTATCSEQ.ID NO. 222 CTGGCTGGTGACCTGCTTTGAGTA SEQ.ID NO. 223TAGGCGCGCCTGACATACAGCAATGCCAGTT SEQ.ID NO. 224TAAGAATGCGGCCGCGCCACATCTTGAACACTTTGC SEQ.ID NO. 225TGGGGAGGAGTTTGAGGAGCAGAC SEQ.ID NO. 226 GTGGGACGGAGGGGGCAGTGAAGSEQ.ID NO. 227 GCAACTATTCGGAGCGCGTG SEQ.ID NO. 228 CCAGCAGCTTGTTGAGCTCCSEQ.ID NO. 229 GGAGGAGCTAAGCGTCATCGC SEQ.ID NO. 230 TCGCTTCAGCGCGTAGACCSEQ.ID NO. 231 TATTAGTTGGGATGGTGGTAGCAC SEQ.ID NO. 232GAGAATTCGAGTCGACGATGAC SEQ.ID NO. 233 GAAATTGTGTTGACGCAGTCTCCSEQ.ID NO. 234 AGGCACACAACAGAGGCAGTTC SEQ.ID NO. 235GTACATCAACCTCCTGCTGTCC SEQ.ID NO. 236 GACATCTCCAAGTCCCAGCATGSEQ.ID NO. 237 AGTCTCTCACTGTGCCTTATGCC SEQ.ID NO. 238AGTCCTAAGAACTGTAAACG SEQ.ID NO. 239 CATCTATACGTGGATTGAGGA SEQ.ID NO. 240ATAGGTACCAGGTATGAGCTG SEQ.ID NO. 241 TGTCCACATCATCATCGTCATCCSEQ.ID NO. 242 TGTCACTGGTCGGTCGCTGAGG SEQ.ID NO. 243 CATGGGGCTTAAGATGTCSEQ.ID NO. 244 GTCGATTTCTCCATCATCTG SEQ.ID NO. 245 AAGAGGCGCTCTACTAGCCGSEQ.ID NO. 246 CTTTCCACATGGAACACAGG SEQ.ID NO. 247CATTTTCCTGGAATTTGATACAG SEQ.ID NO. 248 GTAGAGAGTTTATTTGGGCCAAGSEQ.ID NO. 249 CATCTATGGTAACTACAATCG SEQ.ID NO. 250GTAGAAGTCACTGATCAGACAC SEQ.ID NO. 251 CTGCCTGCCAACCTTTCCATTTCTSEQ.ID NO. 252 TGAGCAGCCACAGCAGCATTAGG SEQ.ID NO. 253CACCTGATCAGGTGGATAAGG SEQ.ID NO. 254 TCCCAGGTAGAAGGTGGAATCC

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1-93. (canceled)
 94. An isolated or purified antibody or anantigen-binding fragment thereof capable of specifically binding to apolypeptide selected from the group consisting of; a) a polypeptidecomprising the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1),and; b) a polypeptide comprising a sequence encoded by SEQ ID NO.:24 ora fragment of at least 6 amino acids of said polypeptide. 95-96.(canceled)
 97. An hybridoma cell producing the antibody or antigenbinding fragment thereof of claim
 94. 98-99. (canceled)
 100. Acomposition comprising the antibody or antigen binding fragment thereofof claim
 94. 101. A method of making an antibody comprising immunizing anon-human animal with an immunogenic fragment of a polypeptide selectedfrom the group consisting of a. a polypeptide comprising the amino acidsequence set forth in SEQ ID NO.:70 (KAAG1), and; b. a polypeptidecomprising a sequence encoded by SEQ ID NO.:24. 102-124. (canceled) 125.A method of treating cancer comprising administering an antibody or anantigen binding fragment thereof capable of specific binding to apolypeptide selected from the group consisting of a. a polypeptidecomprising the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1) b.a polypeptide encoded by SEQ ID NO.:24, c. a fragment of any one of a)or b), d. a derivative of any one of a) or b) and; e. an analog of anyone of a) or b). to a mammal in need.
 126. (canceled)
 127. The antibodyor antigen binding fragment thereof of claim 94, wherein the antibody orantigen binding fragment thereof is linked to a toxin.
 128. Thecomposition of claim 100, wherein the antibody or antigen bindingfragment thereof is linked to a toxin.
 129. A method of treating cancer,the method comprising administering a toxin-linked antibody or antigenbinding fragment thereof that specifically binds to a polypeptide havingthe amino acid sequence set forth in SEQ ID NO.:70 (KAAG1) to a cancerpatient having a) ovarian cancer, prostate cancer, renal cancer, lungcancer, colon cancer, breast cancer, central nervous system cancer,leukemia or melanoma comprising cancer cells expressing the polypeptideand b) normal kidney cells that do not express KAAG1, wherein thetoxin-linked antibody or antigen binding fragment thereof comprisescomplementarity determining regions identical to those of a monoclonalantibody, chimeric antibody, humanized antibody, human antibody or of aFab fragment thereof that specifically binds to the polypeptide andwherein the toxin is toxic to the cancer cells.
 130. The method of claim129, wherein the cancer patient is selected prior to administration forhaving a) ovarian cancer, prostate cancer, renal cancer, lung cancer,colon cancer, breast cancer, central nervous system cancer, leukemia ormelanoma comprising cancer cells expressing a polypeptide having theamino acid sequence set forth in SEQ ID NO.:70 (KAAG1) and b) normalkidney cells that do not express KAAG1.
 131. The method of claim 129,wherein the method is for treating ovarian cancer in a cancer patientsuffering from ovarian cancer.
 132. The method of claim 131, wherein theovarian cancer is late stage ovarian cancer.
 133. A method of inhibitingthe growth or survival of cancer cells, the method comprisingadministering a toxin-linked antibody or antigen binding fragmentthereof that specifically binds to a polypeptide having the amino acidsequence set forth in SEQ ID NO.:70 (KAAG1) to a cancer patient havinga) a cancer comprising cancer cells expressing the polypeptide and b)normal kidney cells that do not express KAAG1, wherein the toxin-linkedantibody or antigen binding fragment thereof comprises complementaritydetermining regions identical to those of a monoclonal antibody,chimeric antibody, humanized antibody, human antibody or of a Fabfragment thereof that specifically binds to the polypeptide and whereinthe toxin is toxic to the cancer cells.